practical research review of related literature

Have a language expert improve your writing

Run a free plagiarism check in 10 minutes, generate accurate citations for free.

• Knowledge Base

Methodology

• How to Write a Literature Review | Guide, Examples, & Templates

How to Write a Literature Review | Guide, Examples, & Templates

Published on January 2, 2023 by Shona McCombes . Revised on September 11, 2023.

What is a literature review? A literature review is a survey of scholarly sources on a specific topic. It provides an overview of current knowledge, allowing you to identify relevant theories, methods, and gaps in the existing research that you can later apply to your paper, thesis, or dissertation topic .

There are five key steps to writing a literature review:

• Search for relevant literature
• Evaluate sources
• Identify themes, debates, and gaps
• Outline the structure
• Write your literature review

A good literature review doesn’t just summarize sources—it analyzes, synthesizes , and critically evaluates to give a clear picture of the state of knowledge on the subject.

Instantly correct all language mistakes in your text

Upload your document to correct all your mistakes in minutes

Table of contents

What is the purpose of a literature review, examples of literature reviews, step 1 – search for relevant literature, step 2 – evaluate and select sources, step 3 – identify themes, debates, and gaps, step 4 – outline your literature review’s structure, step 5 – write your literature review, free lecture slides, other interesting articles, frequently asked questions, introduction.

• Quick Run-through
• Step 1 & 2

When you write a thesis , dissertation , or research paper , you will likely have to conduct a literature review to situate your research within existing knowledge. The literature review gives you a chance to:

• Demonstrate your familiarity with the topic and its scholarly context
• Develop a theoretical framework and methodology for your research
• Position your work in relation to other researchers and theorists
• Show how your research addresses a gap or contributes to a debate
• Evaluate the current state of research and demonstrate your knowledge of the scholarly debates around your topic.

Writing literature reviews is a particularly important skill if you want to apply for graduate school or pursue a career in research. We’ve written a step-by-step guide that you can follow below.

Receive feedback on language, structure, and formatting

Professional editors proofread and edit your paper by focusing on:

• Academic style
• Vague sentences
• Style consistency

See an example

Writing literature reviews can be quite challenging! A good starting point could be to look at some examples, depending on what kind of literature review you’d like to write.

• Example literature review #1: “Why Do People Migrate? A Review of the Theoretical Literature” ( Theoretical literature review about the development of economic migration theory from the 1950s to today.)
• Example literature review #2: “Literature review as a research methodology: An overview and guidelines” ( Methodological literature review about interdisciplinary knowledge acquisition and production.)
• Example literature review #3: “The Use of Technology in English Language Learning: A Literature Review” ( Thematic literature review about the effects of technology on language acquisition.)
• Example literature review #4: “Learners’ Listening Comprehension Difficulties in English Language Learning: A Literature Review” ( Chronological literature review about how the concept of listening skills has changed over time.)

You can also check out our templates with literature review examples and sample outlines at the links below.

Download Word doc Download Google doc

Before you begin searching for literature, you need a clearly defined topic .

If you are writing the literature review section of a dissertation or research paper, you will search for literature related to your research problem and questions .

Make a list of keywords

Start by creating a list of keywords related to your research question. Include each of the key concepts or variables you’re interested in, and list any synonyms and related terms. You can add to this list as you discover new keywords in the process of your literature search.

• Social media, Facebook, Instagram, Twitter, Snapchat, TikTok
• Body image, self-perception, self-esteem, mental health
• Generation Z, teenagers, adolescents, youth

Search for relevant sources

Use your keywords to begin searching for sources. Some useful databases to search for journals and articles include:

• Your university’s library catalogue
• Google Scholar
• Project Muse (humanities and social sciences)
• Medline (life sciences and biomedicine)
• EconLit (economics)
• Inspec (physics, engineering and computer science)

You can also use boolean operators to help narrow down your search.

Make sure to read the abstract to find out whether an article is relevant to your question. When you find a useful book or article, you can check the bibliography to find other relevant sources.

You likely won’t be able to read absolutely everything that has been written on your topic, so it will be necessary to evaluate which sources are most relevant to your research question.

For each publication, ask yourself:

• What question or problem is the author addressing?
• What are the key concepts and how are they defined?
• What are the key theories, models, and methods?
• Does the research use established frameworks or take an innovative approach?
• What are the results and conclusions of the study?
• How does the publication relate to other literature in the field? Does it confirm, add to, or challenge established knowledge?
• What are the strengths and weaknesses of the research?

Make sure the sources you use are credible , and make sure you read any landmark studies and major theories in your field of research.

You can use our template to summarize and evaluate sources you’re thinking about using. Click on either button below to download.

Take notes and cite your sources

As you read, you should also begin the writing process. Take notes that you can later incorporate into the text of your literature review.

It is important to keep track of your sources with citations to avoid plagiarism . It can be helpful to make an annotated bibliography , where you compile full citation information and write a paragraph of summary and analysis for each source. This helps you remember what you read and saves time later in the process.

The only proofreading tool specialized in correcting academic writing - try for free!

The academic proofreading tool has been trained on 1000s of academic texts and by native English editors. Making it the most accurate and reliable proofreading tool for students.

Try for free

To begin organizing your literature review’s argument and structure, be sure you understand the connections and relationships between the sources you’ve read. Based on your reading and notes, you can look for:

• Trends and patterns (in theory, method or results): do certain approaches become more or less popular over time?
• Themes: what questions or concepts recur across the literature?
• Debates, conflicts and contradictions: where do sources disagree?
• Pivotal publications: are there any influential theories or studies that changed the direction of the field?
• Gaps: what is missing from the literature? Are there weaknesses that need to be addressed?

This step will help you work out the structure of your literature review and (if applicable) show how your own research will contribute to existing knowledge.

• Most research has focused on young women.
• There is an increasing interest in the visual aspects of social media.
• But there is still a lack of robust research on highly visual platforms like Instagram and Snapchat—this is a gap that you could address in your own research.

There are various approaches to organizing the body of a literature review. Depending on the length of your literature review, you can combine several of these strategies (for example, your overall structure might be thematic, but each theme is discussed chronologically).

Chronological

The simplest approach is to trace the development of the topic over time. However, if you choose this strategy, be careful to avoid simply listing and summarizing sources in order.

Try to analyze patterns, turning points and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred.

If you have found some recurring central themes, you can organize your literature review into subsections that address different aspects of the topic.

For example, if you are reviewing literature about inequalities in migrant health outcomes, key themes might include healthcare policy, language barriers, cultural attitudes, legal status, and economic access.

Methodological

If you draw your sources from different disciplines or fields that use a variety of research methods , you might want to compare the results and conclusions that emerge from different approaches. For example:

• Look at what results have emerged in qualitative versus quantitative research
• Discuss how the topic has been approached by empirical versus theoretical scholarship
• Divide the literature into sociological, historical, and cultural sources

Theoretical

A literature review is often the foundation for a theoretical framework . You can use it to discuss various theories, models, and definitions of key concepts.

You might argue for the relevance of a specific theoretical approach, or combine various theoretical concepts to create a framework for your research.

Like any other academic text , your literature review should have an introduction , a main body, and a conclusion . What you include in each depends on the objective of your literature review.

The introduction should clearly establish the focus and purpose of the literature review.

Depending on the length of your literature review, you might want to divide the body into subsections. You can use a subheading for each theme, time period, or methodological approach.

As you write, you can follow these tips:

• Summarize and synthesize: give an overview of the main points of each source and combine them into a coherent whole
• Analyze and interpret: don’t just paraphrase other researchers — add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
• Critically evaluate: mention the strengths and weaknesses of your sources
• Write in well-structured paragraphs: use transition words and topic sentences to draw connections, comparisons and contrasts

In the conclusion, you should summarize the key findings you have taken from the literature and emphasize their significance.

When you’ve finished writing and revising your literature review, don’t forget to proofread thoroughly before submitting. Not a language expert? Check out Scribbr’s professional proofreading services !

This article has been adapted into lecture slides that you can use to teach your students about writing a literature review.

Scribbr slides are free to use, customize, and distribute for educational purposes.

Open Google Slides Download PowerPoint

If you want to know more about the research process , methodology , research bias , or statistics , make sure to check out some of our other articles with explanations and examples.

• Sampling methods
• Simple random sampling
• Stratified sampling
• Cluster sampling
• Likert scales
• Reproducibility

 Statistics

• Null hypothesis
• Statistical power
• Probability distribution
• Effect size
• Poisson distribution

Research bias

• Optimism bias
• Cognitive bias
• Implicit bias
• Hawthorne effect
• Anchoring bias
• Explicit bias

A literature review is a survey of scholarly sources (such as books, journal articles, and theses) related to a specific topic or research question .

It is often written as part of a thesis, dissertation , or research paper , in order to situate your work in relation to existing knowledge.

There are several reasons to conduct a literature review at the beginning of a research project:

• To familiarize yourself with the current state of knowledge on your topic
• To ensure that you’re not just repeating what others have already done
• To identify gaps in knowledge and unresolved problems that your research can address
• To develop your theoretical framework and methodology
• To provide an overview of the key findings and debates on the topic

Writing the literature review shows your reader how your work relates to existing research and what new insights it will contribute.

The literature review usually comes near the beginning of your thesis or dissertation . After the introduction , it grounds your research in a scholarly field and leads directly to your theoretical framework or methodology .

A literature review is a survey of credible sources on a topic, often used in dissertations , theses, and research papers . Literature reviews give an overview of knowledge on a subject, helping you identify relevant theories and methods, as well as gaps in existing research. Literature reviews are set up similarly to other  academic texts , with an introduction , a main body, and a conclusion .

An  annotated bibliography is a list of  source references that has a short description (called an annotation ) for each of the sources. It is often assigned as part of the research process for a  paper .  

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the “Cite this Scribbr article” button to automatically add the citation to our free Citation Generator.

McCombes, S. (2023, September 11). How to Write a Literature Review | Guide, Examples, & Templates. Scribbr. Retrieved April 15, 2024, from https://www.scribbr.com/dissertation/literature-review/

Is this article helpful?

Shona McCombes

Other students also liked, what is a theoretical framework | guide to organizing, what is a research methodology | steps & tips, how to write a research proposal | examples & templates, what is your plagiarism score.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Indian J Sex Transm Dis AIDS
• v.35(2); Jul-Dec 2014

Reviewing literature for research: Doing it the right way

Shital amin poojary.

Department of Dermatology, K J Somaiya Medical College, Mumbai, Maharashtra, India

Jimish Deepak Bagadia

In an era of information overload, it is important to know how to obtain the required information and also to ensure that it is reliable information. Hence, it is essential to understand how to perform a systematic literature search. This article focuses on reliable literature sources and how to make optimum use of these in dermatology and venereology.

INTRODUCTION

A thorough review of literature is not only essential for selecting research topics, but also enables the right applicability of a research project. Most importantly, a good literature search is the cornerstone of practice of evidence based medicine. Today, everything is available at the click of a mouse or at the tip of the fingertips (or the stylus). Google is often the Go-To search website, the supposed answer to all questions in the universe. However, the deluge of information available comes with its own set of problems; how much of it is actually reliable information? How much are the search results that the search string threw up actually relevant? Did we actually find what we were looking for? Lack of a systematic approach can lead to a literature review ending up as a time-consuming and at times frustrating process. Hence, whether it is for research projects, theses/dissertations, case studies/reports or mere wish to obtain information; knowing where to look, and more importantly, how to look, is of prime importance today.

Literature search

Fink has defined research literature review as a “systematic, explicit and reproducible method for identifying, evaluating, and synthesizing the existing body of completed and recorded work produced by researchers, scholars and practitioners.”[ 1 ]

Review of research literature can be summarized into a seven step process: (i) Selecting research questions/purpose of the literature review (ii) Selecting your sources (iii) Choosing search terms (iv) Running your search (v) Applying practical screening criteria (vi) Applying methodological screening criteria/quality appraisal (vii) Synthesizing the results.[ 1 ]

This article will primarily concentrate on refining techniques of literature search.

Sources for literature search are enumerated in Table 1 .

Sources for literature search

PubMed is currently the most widely used among these as it contains over 23 million citations for biomedical literature and has been made available free by National Center for Biotechnology Information (NCBI), U.S. National Library of Medicine. However, the availability of free full text articles depends on the sources. Use of options such as advanced search, medical subject headings (MeSH) terms, free full text, PubMed tutorials, and single citation matcher makes the database extremely user-friendly [ Figure 1 ]. It can also be accessed on the go through mobiles using “PubMed Mobile.” One can also create own account in NCBI to save searches and to use certain PubMed tools.

PubMed home page showing location of different tools which can be used for an efficient literature search

Tips for efficient use of PubMed search:[ 2 , 3 , 4 ]

Use of field and Boolean operators

When one searches using key words, all articles containing the words show up, many of which may not be related to the topic. Hence, the use of operators while searching makes the search more specific and less cumbersome. Operators are of two types: Field operators and Boolean operators, the latter enabling us to combine more than one concept, thereby making the search highly accurate. A few key operators that can be used in PubMed are shown in Tables ​ Tables2 2 and ​ and3 3 and illustrated in Figures ​ Figures2 2 and ​ and3 3 .

Field operators used in PubMed search

Boolean operators used in PubMed search

PubMed search results page showing articles on donovanosis using the field operator [TIAB]; it shows all articles which have the keyword “donovanosis” in either title or abstract of the article

PubMed search using Boolean operators ‘AND’, ‘NOT’; To search for articles on treatment of lepra reaction other than steroids, after clicking the option ‘Advanced search’ on the home page, one can build the search using ‘AND’ option for treatment and ‘NOT’ option for steroids to omit articles on steroid treatment in lepra reaction

Use of medical subject headings terms

These are very specific and standardized terms used by indexers to describe every article in PubMed and are added to the record of every article. A search using MeSH will show all articles about the topic (or keywords), but will not show articles only containing these keywords (these articles may be about an entirely different topic, but still may contain your keywords in another context in any part of the article). This will make your search more specific. Within the topic, specific subheadings can be added to the search builder to refine your search [ Figure 4 ]. For example, MeSH terms for treatment are therapy and therapeutics.

PubMed search using medical subject headings (MeSH) terms for management of gonorrhea. Click on MeSH database ( Figure 1 ) →In the MeSH search box type gonorrhea and click search. Under the MeSH term gonorrhea, there will be a list of subheadings; therapy, prevention and control, click the relevant check boxes and add to search builder →Click on search →All articles on therapy, prevention and control of gonorrhea will be displayed. Below the subheadings, there are two options: (1) Restrict to medical subject headings (MeSH) major topic and (2) do not include MeSH terms found below this term in the MeSH hierarchy. These can be used to further refine the search results so that only articles which are majorly about treatment of gonorrhea will be displayed

Two additional options can be used to further refine MeSH searches. These are located below the subheadings for a MeSH term: (1) Restrict to MeSH major topic; checking this box will retrieve articles which are majorly about the search term and are therefore, more focused and (2) Do not include MeSH terms found below this term in the MeSH hierarchy. This option will again give you more focused articles as it excludes the lower specific terms [ Figure 4 ].

Similar feature is available with Cochrane library (also called MeSH), EMBASE (known as EMTREE) and PsycINFO (Thesaurus of Psychological Index Terms).

Saving your searches

Any search that one has performed can be saved by using the ‘Send to’ option and can be saved as a simple word file [ Figure 5 ]. Alternatively, the ‘Save Search’ button (just below the search box) can be used. However, it is essential to set up an NCBI account and log in to NCBI for this. One can even choose to have E-mail updates of new articles in the topic of interest.

Saving PubMed searches. A simple option is to click on the dropdown box next to ‘Send to’ option and then choose among the options. It can be saved as a text or word file by choosing ‘File’ option. Another option is the “Save search” option below the search box but this will require logging into your National Center for Biotechnology Information account. This however allows you to set up alerts for E-mail updates for new articles

Single citation matcher

This is another important tool that helps to find the genuine original source of a particular research work (when few details are known about the title/author/publication date/place/journal) and cite the reference in the most correct manner [ Figure 6 ].

Single citation matcher: Click on “Single citation matcher” on PubMed Home page. Type available details of the required reference in the boxes to get the required citation

Full text articles

In any search clicking on the link “free full text” (if present) gives you free access to the article. In some instances, though the published article may not be available free, the author manuscript may be available free of charge. Furthermore, PubMed Central articles are available free of charge.

Managing filters

Filters can be used to refine a search according to type of article required or subjects of research. One can specify the type of article required such as clinical trial, reviews, free full text; these options are available on a typical search results page. Further specialized filters are available under “manage filters:” e.g., articles confined to certain age groups (properties option), “Links” to other databases, article specific to particular journals, etc. However, one needs to have an NCBI account and log in to access this option [ Figure 7 ].

Managing filters. Simple filters are available on the ‘search results’ page. One can choose type of article, e.g., clinical trial, reviews etc. Further options are available in the “Manage filters” option, but this requires logging into National Center for Biotechnology Information account

The Cochrane library

Although reviews are available in PubMed, for systematic reviews and meta-analysis, Cochrane library is a much better resource. The Cochrane library is a collection of full length systematic reviews, which can be accessed for free in India, thanks to Indian Council of Medical Research renewing the license up to 2016, benefitting users all over India. It is immensely helpful in finding detailed high quality research work done in a particular field/topic [ Figure 8 ].

Cochrane library is a useful resource for reliable, systematic reviews. One can choose the type of reviews required, including trials

An important tool that must be used while searching for research work is screening. Screening helps to improve the accuracy of search results. It is of two types: (1) Practical: To identify a broad range of potentially useful studies. Examples: Date of publication (last 5 years only; gives you most recent updates), participants or subjects (humans above 18 years), publication language (English only) (2) methodological: To identify best available studies (for example, excluding studies not involving control group or studies with only randomized control trials).

Selecting the right quality of literature is the key to successful research literature review. The quality can be estimated by what is known as “The Evidence Pyramid.” The level of evidence of references obtained from the aforementioned search tools are depicted in Figure 9 . Systematic reviews obtained from Cochrane library constitute level 1 evidence.

Evidence pyramid: Depicting the level of evidence of references obtained from the aforementioned search tools

Thus, a systematic literature review can help not only in setting up the basis of a good research with optimal use of available information, but also in practice of evidence-based medicine.

Source of Support: Nil.

Conflict of Interest: None declared.

Lesson 22: Review of Related Literature (RRL)

Meaning of Review of Related Literature

Literature is an oral or written record of man’s significant experiences that are artistically conveyed in a prosaic manner. Embodied in any literary work like essay, novel, journal, story, biography, etc. are man’s best thoughts and feelings about the world. These recorded or preserved world perceptions of man are expressed directly and indirectly. Direct expressions of man’s knowledge of the world are in books, periodicals, and online reading materials. Indirect expressions are his inferences or reflections of his surroundings that are not written or spoken at all. (Ridley 2012)

A review of related literature is an analysis of man’s written or spoken knowledge of the world. You examine representations of man’s thinking about the world to determine the connection of your research with what people already know about it. In your analysis or reading of recorded knowledge, you just do not catalog ideas in your research paper, but also interpret them or merge your thinking with the author’s ideas.

Hence, in doing the RRL, you deal with both formal or direct and informal or indirect expressions of man’s knowledge. Fusing your world understanding with the authors’ world perceptions enables you to get a good analysis of existing written works that are related to your research study. (Wallman 2014)

Purposes of Review of Related Literature (RRL)

1.     To obtain background knowledge of your research

2.     To relate your study to the current condition or situation of the world

3.     To show the capacity of your research work to introduce new knowledge

4.     To expand, prove, or disprove the findings of previous research studies

5.     To increase your understanding of the underlying theories, principles, or concepts of your research

6.     To explain technical terms involved in your research study

7.     To highlight the significance of your work with the kind of evidence it gathered to support the conclusion of your research

8.     To avoid repeating previous research studies

9.     To recommend the necessity of further research on a certain topic

Styles or Approaches of RRL or Review of Related Literature

1. Traditional Review of Literature

To do a review of literature in a traditional way is to summarize present forms of knowledge on a specific subject. Your aim here is to give an expanded or new understanding of an existing work. Being necessarily descriptive, interpretative, evaluative, and methodically unclear and uncertain, a traditional review is prone to your subjectivity. This kind of review does not require you to describe your method of reviewing literature but expects you to state your intentions in conducting the review and to name the sources of information.

You experience much freedom or flexibility in doing a traditional RRL, so as an undergraduate student taking BA, BSE, BSEED, or any four-year bachelor degree and lacking much knowledge and expertise in research work, this is the appropriate method for you. Attaining mastery in doing a traditional RRL is an excellent preparation for the more demanding, second style of RRL called systematic review that is required at the graduate level.

Hence, being unprepared for a systematic review, you have no other way but to do the traditional review to complete the requirements of your course. (Jesson 2011)

Traditional review is of different types that are as follows:

1.     Conceptual review – analysis of concepts or ideas to give meaning to some national or world issues

2.     Critical review – focuses on theories or hypotheses and examines meanings and results of their application to situations

3.     State-of-the-Art review – makes the researcher deal with the latest research studies on the subject

4.     Expert review – encourages a well-known expert to do the RRL because of the influence of a certain ideology, paradigm, or belief on him/her

5.     Scoping review – prepares a situation for a future research work in the form of project making about community development, government policies, and health services, among others

2. Systematic Review of Literature

As indicated by its name, systematic, which means methodical, is a style of RRL that involves sequential acts of a review of related literature. Unlike  the traditional review that has no particular method, systematic review requires you to go through the following RRL steps (Ridley 2012):

1.     Have a clear understanding of the research questions. Serving as the compass to direct your research activities, the research questions tell you what to collect and where to obtain those data you want to collect.

2.     Plan your manner of obtaining the data. Imagining how you will get to where the data are, you will come to think also of what keywords to use for easy searching and how to accord courtesy and respect to people or institutions from where the data will come such as planning how to communicate your request to these sources of data.

3.     Do the literature search. Using keywords, you look for the needed information from all sources of knowledge: Internet, books, journals periodicals, government publications, general references, and the like.

4.     Using a certain standard, determine which data, studies, or sources of knowledge are valuable or not to warrant the reasonableness of your decision to take some data and junk the rest.

5.     Determine the methodological soundness of the research studies . Use a checklist or a certain set of criteria in assessing the ways researchers conduct their studies to arrive at a certain conclusion.

6.     Summarize what you have gathered from various sources of data. To concisely present a synthesis of your report, use a graph such as a table and other presentation formats that are not prone to verbosity.

A systematic review of literature is a rigorous way of obtaining data from written works. It is a bias-free style that every researcher wanting to be a research expert should experience. Limiting itself to peer-reviewed journals, academically written works, and quantitative assessment of data through statistical methods, this style of literature review ensures objectivity in every stage of the research. (Fraenbell 2012)

Structure of the RRL

The structure of the whole literature review indicates the organizational pattern or order of the components of the summary of the RRL results.

For the traditional review , the structure of the summary resembles that of an essay where series of united sentences presents the RRL results. However, this structure of traditional review varies based on your subject and area of specialization.

For the systematic review , the structure is based on the research questions; so much so, that, if your RRL does not adhere to a certain method to make you begin your RRL with research questions, your RRL is headed toward a traditional literature review structure.

Regardless of what RRL structure you use, you must see to it that the organizational pattern of the results of your review contains these three elements:

1.     An introduction to explain the organizational method of your literature review,

2.     Headings and subheadings to indicate the right placement of your supporting statements and,

3.     A summary to concisely restate your main point. (Ridley 2013)

You are using an outdated browser. Upgrade your browser today or install Google Chrome Frame to better experience this site.

Related Resources

• —Nature of Inquiry and Research

Self-Learning Module- Quarter 1 Practical Research 2: SHS Modules 1-3 View Download

Self Learning Module  |  ZIP

Curriculum Information

Copyright information, technical information.

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• 16 April 2024

Structure peer review to make it more robust

• Mario Malički 0

Mario Malički is associate director of the Stanford Program on Research Rigor and Reproducibility (SPORR) and co-editor-in-chief of the Research Integrity and Peer Review journal.

You can also search for this author in PubMed   Google Scholar

You have full access to this article via your institution.

In February, I received two peer-review reports for a manuscript I’d submitted to a journal. One report contained 3 comments, the other 11. Apart from one point, all the feedback was different. It focused on expanding the discussion and some methodological details — there were no remarks about the study’s objectives, analyses or limitations.

My co-authors and I duly replied, working under two assumptions that are common in scholarly publishing: first, that anything the reviewers didn’t comment on they had found acceptable for publication; second, that they had the expertise to assess all aspects of our manuscript. But, as history has shown, those assumptions are not always accurate (see Lancet 396 , 1056; 2020 ). And through the cracks, inaccurate, sloppy and falsified research can slip.

As co-editor-in-chief of the journal Research Integrity and Peer Review (an open-access journal published by BMC, which is part of Springer Nature), I’m invested in ensuring that the scholarly peer-review system is as trustworthy as possible. And I think that to be robust, peer review needs to be more structured. By that, I mean that journals should provide reviewers with a transparent set of questions to answer that focus on methodological, analytical and interpretative aspects of a paper.

For example, editors might ask peer reviewers to consider whether the methods are described in sufficient detail to allow another researcher to reproduce the work, whether extra statistical analyses are needed, and whether the authors’ interpretation of the results is supported by the data and the study methods. Should a reviewer find anything unsatisfactory, they should provide constructive criticism to the authors. And if reviewers lack the expertise to assess any part of the manuscript, they should be asked to declare this.

Anonymizing peer review makes the process more just

Other aspects of a study, such as novelty, potential impact, language and formatting, should be handled by editors, journal staff or even machines, reducing the workload for reviewers.

The list of questions reviewers will be asked should be published on the journal’s website, allowing authors to prepare their manuscripts with this process in mind. And, as others have argued before, review reports should be published in full. This would allow readers to judge for themselves how a paper was assessed, and would enable researchers to study peer-review practices.

To see how this works in practice, since 2022 I’ve been working with the publisher Elsevier on a pilot study of structured peer review in 23 of its journals, covering the health, life, physical and social sciences. The preliminary results indicate that, when guided by the same questions, reviewers made the same initial recommendation about whether to accept, revise or reject a paper 41% of the time, compared with 31% before these journals implemented structured peer review. Moreover, reviewers’ comments were in agreement about specific parts of a manuscript up to 72% of the time ( M. Malički and B. Mehmani Preprint at bioRxiv https://doi.org/mrdv; 2024 ). In my opinion, reaching such agreement is important for science, which proceeds mainly through consensus.

Stop the peer-review treadmill. I want to get off

I invite editors and publishers to follow in our footsteps and experiment with structured peer reviews. Anyone can trial our template questions (see go.nature.com/4ab2ppc ), or tailor them to suit specific fields or study types. For instance, mathematics journals might also ask whether referees agree with the logic or completeness of a proof. Some journals might ask reviewers if they have checked the raw data or the study code. Publications that employ editors who are less embedded in the research they handle than are academics might need to include questions about a paper’s novelty or impact.

Scientists can also use these questions, either as a checklist when writing papers or when they are reviewing for journals that don’t apply structured peer review.

Some journals — including Proceedings of the National Academy of Sciences , the PLOS family of journals, F1000 journals and some Springer Nature journals — already have their own sets of structured questions for peer reviewers. But, in general, these journals do not disclose the questions they ask, and do not make their questions consistent. This means that core peer-review checks are still not standardized, and reviewers are tasked with different questions when working for different journals.

Some might argue that, because different journals have different thresholds for publication, they should adhere to different standards of quality control. I disagree. Not every study is groundbreaking, but scientists should view quality control of the scientific literature in the same way as quality control in other sectors: as a way to ensure that a product is safe for use by the public. People should be able to see what types of check were done, and when, before an aeroplane was approved as safe for flying. We should apply the same rigour to scientific research.

Ultimately, I hope for a future in which all journals use the same core set of questions for specific study types and make all of their review reports public. I fear that a lack of standard practice in this area is delaying the progress of science.

Nature 628 , 476 (2024)

doi: https://doi.org/10.1038/d41586-024-01101-9

Reprints and permissions

Competing Interests

M.M. is co-editor-in-chief of the Research Integrity and Peer Review journal that publishes signed peer review reports alongside published articles. He is also the chair of the European Association of Science Editors Peer Review Committee.

Related Articles

• Scientific community
• Peer review

Londoners see what a scientist looks like up close in 50 photographs

Career News 18 APR 24

Researchers want a ‘nutrition label’ for academic-paper facts

Nature Index 17 APR 24

Deadly diseases and inflatable suits: how I found my niche in virology research

Spotlight 17 APR 24

Is ChatGPT corrupting peer review? Telltale words hint at AI use

News 10 APR 24

Three ways ChatGPT helps me in my academic writing

Career Column 08 APR 24

Is AI ready to mass-produce lay summaries of research articles?

Nature Index 20 MAR 24

Head of Biology, Bio-island

Head of Biology to lead the discovery biology group.

Guangzhou, Guangdong, China

BeiGene Ltd.

Research Postdoctoral Fellow - MD (Cardiac Surgery)

Houston, Texas (US)

Baylor College of Medicine (BCM)

Director of Mass Spectrometry

Loyola University Chicago, Stritch School of Medicine (SSOM) seeks applicants for a full-time Director of Mass Spectrometry.

Chicago, Illinois

Loyola University of Chicago - Cell and Molecular Physiology Department

Associate or Senior Editor, Nature Biomedical Engineering

Associate Editor or Senior Editor, Nature Biomedical Engineering Location: London, Shanghai and Madrid — Hybrid office and remote working Deadline:...

London (Central), London (Greater) (GB)

Springer Nature Ltd

FACULTY POSITION IN PATHOLOGY RESEARCH

Dallas, Texas (US)

The University of Texas Southwestern Medical Center (UT Southwestern Medical Center)

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Current progress and limitations of research regarding the therapeutic use of adipose-derived stem cells: literature review

• Open access
• Published: 17 April 2024

Cite this article

You have full access to this open access article

• Maksym Skrypnyk   ORCID: orcid.org/0000-0002-9552-4098 1  

Adipose tissue has recently become one of the most promising and predominant sources of mesenchymal stem cells owing to its high accessibility, culturing properties, regenerative potential, and relatively fewer ethical considerations. From the time of the adipose-derived stem cells (ADSCs) discovery, many beneficial properties have been found, including their regenerative, anti-inflammatory, immunomodulatory, and antimicrobial effects. The number of publications and clinical trials using ADSCs has increased significantly worldwide, attesting to the promising nature of the therapeutic properties of ADSCs.

Main body of the abstract

In clinical studies, ADSCs are mainly used to treat wounds, multiple sclerosis, soft tissue trauma, aging, diabetes, Parkinson’s disease, bone and cartilage regeneration, strokes, and spinal cord injuries. Few and insignificant adverse effects after ADSC treatment have been documented, suggesting their relative safety for clinical use. Despite significant progress in ADSC-related studies, several issues are yet to be addressed, including a lack of standardization of ADSC-associated protocols and the methods used to obtain them, inconsistent dosages, small numbers of patients in each treatment group, and variable graft purity. This severely complicates our ability to compare these studies, making the results even of similar studies controversial.

Short conclusion

This review described the current stage of ADSCs-based treatment outcomes and their limitations, associated with standardization of ADSCs.

Avoid common mistakes on your manuscript.

1 Background

Regenerative medicine is a relatively new branch of science that aims to replace aged, damaged, and disease- or trauma-affected tissues and organs, and to stimulate organismal regenerative potential.

Stem cell therapy involves several mechanisms of action. One is direct replacement of damaged cells and tissues [ 1 ]. Another is a paracrine mechanism that involves modulation of the microenvironment, activation of the native immunity, anti-inflammatory effect and prevention of fibrosis development, pain relief through the secretion of cytokines, regulation of cell death, and immunomodulatory effect [ 2 , 3 ]. Stem cell therapy is considered one of the most promising and highly effective treatment methods for several inflammatory diseases, infectious diseases, non-communicable diseases, cancer, age-related pathologies, pediatric diseases and rejuvenation [ 4 , 5 , 6 ].

Despite this, stem cell therapy is still not widespread and is even forbidden in some countries. Based on available data, no more than 15 allogeneic mesenchymal stem cell (MSC) products have been approved worldwide [ 7 ]. Implementation rates of stem-cell-based therapeutic products remain low, but they have been gradually increasing; as of 17 August 2022, twenty-four cellular and gene therapy products have been licensed by the Office of Tissues and Advanced Therapies (USA) [ 8 ]. Medical tourism to seek stem-cell-based therapies has increased significantly despite the small number of clinical studies and poor evidence base for such therapies [ 7 , 9 ].

Initially MSCs were first found in bone marrow in 1976. It has been shown that MSCs, which are multipotent, can differentiate into mesenchymal, endodermal, and ectodermal cell lines [ 10 ]. Bone marrow is the gold-standard source of MSCs [ 11 ]. The most common harvesting site for bone marrow is the iliac crest, followed by the proximal femur [ 12 ]. However, bone marrow aspiration has significant drawbacks due to its high invasiveness and low MSCs yield [ 13 ]. Even MSCs harvested from different bones of the same individual differ in terms of their regenerative potential and cell concentration, and their effects vary between in-vivo and in-vitro settings [ 14 ]. Bone marrow biopsy is poorly tolerated by patients because of post-procedure pain, and most patients experience anxiety before and during the procedure, even in the case of experienced bone marrow donors [ 15 , 16 ]. Owing to these limitations, alternative MSC donor sites and new approaches are in high demand. Connective tissue and stromal components of inner organs are graft-rich sources for MSCs isolation. One of these is adipose tissue, which is in abundance in a human body. The high proliferation and differentiation capacity of adipose-derived stem cells (ADSCs) and their more accessible donor sites make them a more promising and less invasive alternative to bone-marrow MSCs (BM-MSCs) for stem-cell-based therapies [ 17 ]. ADSCs and BM-MSCs have similar characteristics in terms of their morphology, properties, and receptors[ 18 ]. There are also other sources of adult tissue-derived MSC such as peripheral blood, endometrium, tooth pulp, and breast milk [ 19 ]. Umbilical cord, cord blood, placenta and amniotic fluid are the neonatal sources of stem cells [ 20 ]. Adult and neonatal stem cells have various clinical applications and their own advantages and disadvantages. Neonatal stem cells have higher proliferative capacity, potential growth by multi-layering due to the absence of contact inhibition, no senescence over passaging and lower immunogenicity, and higher immunosuppressive capacity [ 20 ]. Despite possessing better immunological properties, neonatal stem cells have several disadvantages that limit their clinical application such as low cell amount in a single cord blood unit, single time collection, high storage cost etc. [ 21 ].

In most circumstances, only the allogeneic application of neonatal stem cells is possible, while BM-MSCs, ADSCs and peripheral blood stem cells can also be used in autologous settings, which significantly facilitates ethical issues, prevents infections from spreading, and provides a limitless source of cells [ 22 ]. Moreover, BM-MSCs are not immune-privileged and have immunogenic potential in allogeneic settings [ 23 ]. Two strategies exist for prolonging their persistence and improving the efficacy of stem cell therapy: modifying the host immune system response or modifying the antigen properties of MSCs [ 24 ].

The range of application of stem cells-based treatment in clinical medicine expands every year, especially adipose tissue as one of the favorable sources of stem cells found a broad application in tissues engineering [ 25 , 26 ]. This review aims to summarize current understandings of ADSC biology, to discuss the latest ADSC-based experimental studies and clinical trials, and to highlight the current advantages and limitations of using ADSCs in medicine.

A systematic search in the PubMed and Scopus database was conducted on 12 October 2023 for all studies including ADSCs, BM-MSCs and MSCs. Original articles, review articles, meta-analysis, clinical cases and case series written in English were selected for review. The search strategy included usage of the following terms: “adipose-derived stem cells”, “fat-derived stem cells”, “bone marrow-derived stem cells”, “mesenchymal stem cells” and their synonyms. Retrieved articles, relative to the review topic, were stored in a database and duplicates were removed.

2 Main text

2.1 status of research regarding regenerative medicine using adscs.

ADSCs were first retrieved from lipoaspirates by Zuk et al. in 2001 [ 27 ]. While BM-MSCs were historically discovered earlier than ADSCs, their clinical application is sometimes limited. This is why an alternative source of MSCs is required. One of them is ADSCs that have been intensively studied worldwide owing to their relative ease of isolation, few ethical considerations, non-invasive harvesting procedure, good culturing properties, and promising results in in-vitro and in-vivo research.

Medical stem cell therapy is flourishing worldwide; however, patients sometimes have unsubstantiated expectations regarding stem cell therapy. Sometimes, stem cell treatment is provided without proper indications and has life-threatening consequences [ 28 ]. The high cost of treatment, low quality, long waiting times, jurisdictional legal restrictions, inability to participate in clinical trials, and lack of access to unapproved treatments lead patients to engage in stem cell tourism. The leaders in international MSC tourism are the USA, China, India, Thailand, and Mexico [ 29 ].

In Japan, in addition to laws governing clinical trials conducted under the International Conference on Harmonisation – Good Clinical Practice and the requirement for the approval of regenerative medical products ( Pharmaceutical and Medical Device Act ), the Act on the Safety of Regenerative Medicine governs the implementation of regenerative medicine in clinical trials or as a treatment. Due to the Regenerative Medicine Act all the procedures were classified into risk categories (high, intermediate and low risk, which are Class I, II and III respectively), among which treatment and research using ADSCs are being conducted in various clinical departments, including the orthopedic and dental fields [ 30 ].

Around the world, stem cell therapies, including those using ADSCs, are offered in clinical practice, with the main clinical indications being multiple sclerosis, cellular therapy of cornea injuries, chronic pulmonary disease, rejuvenation, Parkinson's disease, bone and soft tissues augmentation and regeneration which were destroyed due periodontitis, stroke therapy, severe spinal cord injury, cerebral palsy, chronic wound healing, autism, amyotrophic latent arteriosclerosis, Alzheimer's disease, and inflammatory joints disease [ 31 ].

A search of “adipose-derived stem cells” on www.clinicaltrials.gov found that more than 394 clinical trials using ADSCs have been conducted worldwide, 132 of which have already been completed. In clinical trials, ADSCs have been used for face rejuvenation, keloid treatment, reconstructive surgery, alopecia treatment, arthritis therapy, periodontal therapy, diabetic wound healing, and many other purposes.

2.2 Biology of adipose tissue

Adipose tissue is a connective tissue with special properties. Approximately 20–25% percent of a healthy individual’s weight is adipose tissue. Based on morphological differences, adipocytes were distributed into white, brown and bright (beige) adipocytes. Depending on its location, adipose tissue is classified into subcutaneous (located under the skin) or visceral (around inner organs) fat. White adipocytes are found in white adipose tissue (WAT), and cell shape varies from spherical to oval or polyhedral. Almost the entire cell volume is occupied by a unilocular lipid droplet which occupied the central part of an adipocyte and flattens to the periphery nucleus. The adipocyte`s lipid droplets are lost on a histological section during the traditional way of tissues preparation, which gives WAT a thin polygonal mesh appearance [ 32 , 33 ]. Visceral adipose tissue (VAT) presented as abdominal viscera, mesenterium and omentum, has completely different qualities compared to WAT. Adipocytes type, their secretome, endocrine regulation, proliferation rate, lipolytic activity, sensitivity to insulin and other hormones differ between subcutaneous WAT and visceral fat. Macrophages are more prevalent in VAT compared with subcutaneous WAT [ 34 ].

Brown adipose tissue is common in newborns and located in the neck, back and shoulder areas. With maturation, brown fat scatters around the body. In adults it is located around the neck and inner organs such as the kidneys, adrenal glands, aorta and mediastinum. Brown adipocytes are much smaller compared to white and beige adipocytes, and their lipids are distributed into numerous lipid droplets, with their nucleus located at the cell center. These cells are abundant in mitochondria, with a brown appearance. The major function of these cells is to produce heat. There are two types of brown adipocytes: high- and low-thermogenic adipocytes [ 35 ].

Beige adipocytes are a recently discovered type of brown adipocyte located in subcutaneous fat depots, such as the inguinal and anterior subcutaneous WAT; however, a small number can also be found in VAT [ 36 ]. Beige adipocytes have a multilocular morphology. Properties, cultural and functional differences of white, brown and beige adipocytes summarized in Table  1 .

Similar to every connective tissue, adipose tissue presented as cells surrounded by an extracellular matrix. Cells percentage in adipose tissue is significantly prevail under the extracellular matrix component. Adipocyte is a minimal structural and functional unit of adipose tissue. Besides adipocytes, adipose tissue also consists of preadipocytes, fibroblasts, capillary endothelial cells, macrophages, and stem cells, all of which form the stromal vascular fraction (SVF) that supports, supplies, and protect adipocytes [ 36 ]. Adipose tissue has a good blood supply and is innervated by unmyelinated nerves [ 37 ].

In mammals, adipose tissue has the following important functions: energy storage, hormone secretion, metabolism, protection, and thermogenesis. In recent years, adipose tissue has been considered as a powerful endocrine organ because it produces several hormones such as estrogen, leptin, adiponectin, resistin, and biologically active substances such as TNF, IL-6, IL-1, CCL2, MCP1, PAI-1, and complement factors [ 38 , 39 ].

SVF is one of the adipose tissue components that is a mixture of cells contained within adipocytes that is traditionally isolated by enzymatic digestion. After adipocytes extraction, connective tissue and blood from lipoaspirate, come the SVF, a mix including MSC, endothelial precursor, T-reg, adipose tissue macrophages, smooth muscle cells, pericytes and preadipocytes [ 40 , 41 ].

2.3 Adipose tissue as a source of MSC

WAT is a huge source of MSCs with superior culturing properties. In humans that WAT has an abundance of CD-34+ -cells, immunohistochemical analysis has confirmed that CD-34+ cells are evenly distributed among white adipocytes [ 10 ]. It has been shown that about 5 × 10 5 stem cells can be isolated from a few milligrams of adipose tissue with the possibility of continuously culturing in vitro for up to one month without cell passaging [ 42 ]. Adipose tissue is a prospective source of MSCs owing to variable donor sites, the large quantity of biological sources from deceased donors, and routine deceased-donor workups [ 43 , 44 ]. Studies have shown that WAT harvested from the abdomen of deceased, research-consenting donors indicated that the total nucleated cell count was even higher than that in living donors, and the morphology and functional properties (growth potential, gene expression level, and differentiation ability) of the cell culture were similar [ 43 , 44 ]. However, changes in the properties and biology of adipose tissue in obese individuals are a general health condition [ 39 , 45 , 46 , 47 ]. Isolated ADSCs from VAT and subcutaneous WAT had no differences in morphology and had the same expression of CD antigens. However, the growth rate of subcutaneous WAT ADSCs is 1.75 faster than ADSCs isolated from VAT also ADSCs were different in terms of angiogenic and inflammatory cytokines level. ADSCs from subcutaneous WAT have significantly lower concentrations of chitinase 3-like 1, IL-1β, EGF, MCP-1, Cystatin C, IL-6, IL-8, Pentraxin 3, TGF-β, plasminogen activator urokinase receptor and TNF-α [ 48 ].

There are three main criteria for ADSCs. Firstly, MSCs must have adherent growth; trilineage mesenchymal differentiation (adipocytes, osteoblasts, and chondroblasts). Secondly, ADSCs must express surface specific antigens such as expressing MSCs markers like CD44, CD105, CD90, and CD73, which are progenitors in subcutaneous WAT, and their phenotype is similar to BM-MSCs. Thirdly, ADSCs do not express the HLA-DR protein or MHC Class I molecules, which enable the possibility of allogeneic transplantation [ 49 ].

Some scientists considered that ADSCs to be immune-privileged cells [ 41 ]. The concept of immune privilege means that some biological grafts can survive in the recipient’s body for a certain time without triggering a graft-versus-host response or large-scale destructive inflammation in the place of application [ 50 ]. However, other studies have shown that MSCs are not completely immune-privileged, due to the triggering of both humoral and cellular immune responses in vivo, which depends on the microenvironment [ 24 ]. For example, the second transplantation of allogeneic MSCs from the same donor in mice resulted in accelerated rejection of cells, which attests to the formation of T-cell memory [ 51 ]. It was reported that ADSCs have superior immunomodulatory action because of the less MHC class II expression that makes them a prospective graft material for allogenic treatment [ 52 ]. Allogeneic ADSCs have immunological potential and can trigger graft rejection and inflammation in the recipient’s body. Introducing the human cytomegalovirus US2/US3 gene into ADSCs reduced ADSC immunogenicity and graft rejection by decreasing MHC I protein expression [ 53 ]. This method is promising for obtaining the same effect after transplantation of allogeneic ADSCs as autogenetic ADSCs [ 53 ]. Was reported that immunomodulatory effect related to the regenerative capacity has been increasing [ 52 ]. Moreover, it was shown that MSCs are able to produce molecules which have antimicrobial and analgetic properties, making them a prospective therapeutic agent against cytokine storm- infections [ 54 , 55 ].

Several studies also indicate promising clinical results with brown adipocyte transplantation for the treatment of diabetes and obesity [ 56 ]. In experimental research, brown adipocyte transplantation improved the regulation of adipose tissue and glucose homeostasis as well as insulin resistance [ 57 ]. However, the specific mechanisms behind these effects have not yet been discovered [ 35 ].

2.4 Mechanism of ADSCs action

ADSCs therapy is based on direct replacement of damaged cells with differentiated ADSCs or modification of local paracrine signaling by extracellular vesicles (see Fig.  1 ). Studies report that under different conditions in vitro, ADSCs can differentiate into ectodermal, mesodermal, and endodermal progenitors [ 11 , 17 , 58 , 59 ]. However, only several of these studies reported a successful result in in-vivo studies or clinical trials. Differentiation of ADSCs in vivo is challenging due to poor cell survival, mostly because of the transplantation of cells into organs with a hypoxic environment. However, compared with mature adipocytes, ADSCs have higher survival rates because of less sensitivity to ischemia and secretion of angiogenic factors that stimulate local angiogenesis [ 60 ].

Possible mechanism of ADSCs action via direct cell replacement and paracrine signaling

Studies reported the successful usage of ADSCs in endometrial injury treatment. ADSCs underwent differentiation into mature endometrial epithelial cells, which resulted in endometrial structure and function regeneration [ 61 ]. However, most of studies are limited to the in vitro demonstration of ADSCs differentiation such as differentiation of ADSCs into insulin-producing cells, cells with hepatocytic function, osteocytes, adipocytes etc. [ 58 , 60 , 62 , 63 ]. Nowadays, clinical translation of ADSC-based therapy for a direct cell’s replacement is difficult since most of the mechanisms for stem cells differentiation in the in vivo setting remains unclear. Such treatment might possibly result in the initial stages of cancer development and other adverse results [ 64 ]. ADSCs under inflammation regulate the inflammatory stimuli, triggering the synthesis of pro-angiogenic factors such as VEGF-A, hepatocyte growth factors, and IGF-1 as well as that of hematopoietic cytokines such as macrophage-colony stimulating factor, granulocyte-colony stimulating factor, IL-6, TNF-α [ 65 ].

Another more promising implication of ADSCs is via regulation of local tissue homeostasis. ADSCs possess unique paracrine characteristics. It is realized through extracellular vesicles (EVs) which contain products of cell secretion and transport it to the target cells to regulate cell function and change their phenotype via cell signaling. EVs are secreted by many different cell types, including ADSCs. They contain microRNA, mRNA, lipids, and proteins, and are classified as microvesicles (50–1000 nm in size) and exosomes (30–100 nm)[ 66 , 67 ].

Recently, several promising results of treatment using isolated from ADSCs exosomes were shown. Exosomes of ADSCs contain numerous growths regulating cytokines that enhance recovery of damaged tissue and growth factors that mediate tissue regeneration. These growth factors are: basic fibroblast growth factor, VEGF-A, insulin-like growth factor 1, hepatocyte growth factors, and transforming growth factor, brain-derived neurotrophic factor, nerve growth factor, and glial-derived neurotrophic factor, matrix metalloproteinase- (MMP-) 3 and MMP-9 [ 68 , 69 ].

ADSCs exosomes treatment showed promising results in therapy of neurological diseases, liver fibrosis, myocardial ischemic injuries, endocrine diseases, bone and skin regeneration. Isolated ADSCs exosomes were used for the treatment of ischemic brain injury. They reduced brain ischemia caused by the microglial polarization, which was caused by the delivery of microRNA to inhibit the expression of signal transducers and activators of transcription 1 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) [ 70 ]. Metastasis-associated lung adenocarcinoma transcript 1 was identified as one of the ADSCs exosomes component that contributes to increased neuronal survival and proliferation in traumatic brain injury or other neurodegenerative diseases [ 71 , 72 ]. Mouse ADSC EVs reduced apoptosis of motor neurons of in vitro amyotrophic lateral sclerosis model under the condition of oxidative stress alteration [ 73 ].

Further, exosomes of ADSCs decrease hepatic fibrosis development through the suppression of autophagy, PI3K/AKT/mTOR,,TGF-β/smad, Wnt/β-catenin, LPS/TLR4, EMT/ERK1, PPAR-γ, NF-κB signaling pathways and by the changing of lipid metabolism through regulation of choline metabolism [ 74 , 75 ]. ADSCs exosomes also suppress the proliferation rate of stellate cells through stimulation of apoptosis and arrest of G1 phase of the cell cycle, and through the inhibition of profibrogenic proteins and epithelio-mesenchymal transition [ 76 ]. ADSCs exosome therapy reduced liver damage by downregulation of collagen I, vimentin, α-SMA and fibronectin in liver via selectively transfer of miR-181-5p to affected hepatocytes [ 77 ].

Exosomes isolated from ADSCs are used for the therapy of diabetes mellitus associated erectile dysfunction. They enhance the secretion of the endothelial markers and downregulate caspase-3 after the operation [ 78 ]. ADSCs exosomes activate functional recovery and activate endogenous repair mechanisms of corpus cavernosum via micro RNA 126, 130a and 132 that provides angiogenesis and restore erectile function, and inhibit fibrosis in corpus cavernosum by antifibrotic properties of micro RNA-let7b and c [ 79 ]. Zhao et al. showed that ADSCs exosomes-based treatment induces endometrial regeneration and fertility restoration by collagen remodeling and enhancement of integrin-β3, LIF, and VEGF expression [ 74 ]. EV isolated from human ADSCs increase wound healing and restore the function and prevent scar formation via activation of PI3K/AKT pathway in sebocytes on a murine model [ 80 ].

However, ADSCs and their exosomes have very variable biological properties and cytokine content, even if they were harvested from the SCAT of the same donor but from a different anatomical location. Thus, the thigh fat had a significantly higher cytokines profile except for IL-1β and IL-6, compared with abdominal and chin sites [ 81 ]. Nowadays, standardised issue of ADSC-based therapy, that determine their mechanism of action, is one of a several major limitations of its clinical translation.

2.5 Factors impacting the clinical effectiveness of ADSCs treatment

The result of stem cell treatment depends on the general health of the cell donor. Thus, in patients with diabetes mellitus, type II ADSCs exhibit impaired viability and proliferation rate, mitochondrial dysfunction, senescence phenotype, impaired glucose homeostasis, and insulin sensitivity. Significantly low secretion of VEGF, adiponectin, and CXCL-12, in the background of hypo concentration of leptin, were observed among type-II ADSC samples [ 82 ]. General systemic diseases lead to disturbances in the function and morphology of ADSCs and reduce their therapeutic properties.

Co-transplantation of ADSCs and platelet-rich plasma (PRP) resulted in significantly increased alveolar bone and gingiva regeneration [ 83 , 84 ]. Moreover, PRP activates ADSCs by increasing cytokines and growth factors production, and a fibrin network can be used as a scaffold for the stem cells and to create a conducive microenvironment that increases stemness and prolongs cellular survival rate and duration [ 83 , 85 , 86 ]. Mechanical tension significantly enhances osteoblastic ADSCs differentiation; however, the mitotic activity of ADSCs is not affected by mechanical tension [ 85 ]. Li et al. showed that pretreatment of freshly isolated ADSCs with thymosin beta 4 (Tβ) upregulates the expression of genes associated with cell division, decrease cells doubling time and apoptosis [ 87 ].

In reconstructive surgery, transplantation of ADSCs alone for regenerative purposes is not as effective as co-transplantation with a composition of different cells to create a favorable environment for revascularization, preventing graft resorption and necrosis. In particular, transplantation of ADSCs, adipocytes, and endothelial cells implanted into the extracellular matrix has shown a higher cellular survival rate and volume maintenance when compared to non-prevascularized control grafts [ 86 ].

The injection of ADSCs along with intraoral administration of sildenafil citrate, which enhances blood supply and NO synthesis in animal models, significantly improves the healing rate after colon anastomosis and better reduces inflammation when compared with ADSCs alone [ 88 ]. For promoting hair growth ADSCs pretreated with bee venom is reported to increase the release of fibroblast -1 and -6, endothelial and platelet growth factors and enhancement of cells migration [ 89 ].

The actions of ADSCs are determined by their environment. Human ADSCs transferred to non-inflamed mouse lungs resulted in development of mild low-grade inflammation, which can be associated with apoptotic graft or heterotransplant clearance. T-cells that produce IFNγ can activate the immune response to efferocytosis, thus altering lung homeostasis [ 90 ]. The combination of Shilajit (a herbomineral natural substance) and an alginate hydrogel environment induced osteogenic differentiation of ADSCs into osteoblasts in a short period of time [ 91 ]. Thus, a proper microenvironment can significantly enhance the outcome of ADSCs clinical applications. There are still many concerns about safety of ADSCs therapy, thus, EV from ADSCs showed suppression of breast cancer tumor growth meanwhile the components of cell growth medium had an opposite effect of a tumor [ 92 ].

2.6 Standardization of ADSCs

The translation of novel findings in stem cell therapy to clinical practice has been discouragingly limited and ambiguous, with the effectiveness of some forms of stem cell therapies remaining poorly supported by evidence. The main problem that limits the clinical application of stem cells, in addition to many other biological medical products, is poor standardization and a lack of comprehensive guidelines [ 93 ]. Standardization of biological grafts is necessary because it offers an opportunity to compare research outcomes, which leads to the optimization of ADSC-based treatment.

It is impossible to effectively translate the results of basic research to clinical settings due to differences in cell origins, cultivation conditions, obtainment methods, and the number of cell passages. Tragoonlugkana et al. showed that cell culture plates coated with platelet lysate significantly increased properties of ADSCs such as adhesion, proliferation speed and growth as well as the cells’ viability [ 94 ]. Thus, the same method of adipose tissue harvesting, but used by different commercial systems, influences the cellular content and cytokine secretion of ADSCs [ 95 ]. Distinctive changes in gene expression have been observed after a 48-h ADSCs cultivation period. Regulatory genes are involved in cell morphogenesis and metabolism, cell-to-substrate adhesion, glycoprotein metabolic processes, and regulation of fiber molecular structure organization. Downregulated genes were those involved in cell proliferation, differentiation, and transformation [ 96 ].

Cultural, biological, and functional properties of ADSCs depend on the anatomical location of fat, age, gender, and BMI of patients [ 97 , 98 , 99 ]. It is not yet clear whether isolated cells are actually ADSCs or what types of cells they are able to generate. Researchers agree that not all MSCs have identical characteristics, which can depend on the patient’s age, donor site, isolation technique, and growth [ 100 ]. Close attention should also be paid to the origin of the allogeneic graft, since several studies have underlined that donor age, sex, tissue source, and method of isolation have an effect on cellular and molecular variability [ 101 , 102 ]. Another problem is the safety of the graft and its possibility of being infected with diverse latent viruses that do not trigger a manifestation of the disease under normal conditions. ADSCs harvested from a dog`s omentum with canine distemper disease were found to be infected with canine morbillivirus [ 103 ]. In this study, before the clinical use of ADSCs, cells were checked for the presence of latent viruses.

Currently, the major dilemma with fat grafting, as well as with other biological grafts and substances, is inconsistent results of experimental and clinical findings attributable to poor standardization resulting from wide varieties of harvesting methods, donor sites, and patients’ initial state of health, as well as a lack of established, objective methods for assessment of clinical results and a lack of knowledge on the precise mechanism of stem cell action and regenerative mechanisms. There is also a lack of data and evidence from which to draw conclusions regarding the safety, effectiveness, and impact of ADSCs and other adipose tissue grafts on tissue regeneration [ 104 ].

The main issues that should undergo standardization are adipose tissue harvesting and processing, donor`s health condition, age, cryopreservation and storage procedure, freezing media that was used, quantification of ADSCs number and their phenotypical markers, storage duration, dosage used for the treatment of particular disease etc. Moreover, apart from three main widely accepted criteria for ADSCs – such as plastic-adherent during culturing, trilineage mesenchymal differentiation and expression of specific cell-surface antigens – a functional analysis of ADSCs properties (doubling time, specter and quantity of cytokines secretion, migration speed etc.) should be checked and compared to some standard in order to receive a predictable treatment result.

2.7 Latest clinical studies implementing ADSCs

The number of clinical trials using MSCs has recently significantly increased owing to notable successes and breakthroughs in basic research and experimental studies. New properties and clinical actions of MSCs have been discovered, and their clinical applications and indications have broadened.

Clinical studies have shown that infusion of MSCs leads to vigorous anti-inflammatory effects characterized by lymphocytosis and a decrease in levels of overactivated pro-inflammatory immune cells and TNF-α, in contrast to upregulation of IL-10 secretion. MSCs are known to auto-induce and address their microenvironment to promote cell proliferation and tissue regeneration. MSCs act via paracrine effects on cells and the organ environment, reducing cytokine storms and severe inflammation [ 105 ]. MSCs have been shown to demonstrate antimicrobial properties, increasing the immune response through the production of bactericide peptides and proteins, and the expression of indoleamine 2,3-dioxygenase (enzyme that decrease reproduction rate of viruses, some mammalian cells) and IL-17 [ 106 ]. ADSCs have proven efficient in the treatment of pulmonary diseases in vivo targeting a paracrine pathway, through the promotion of the epitheliocytes mitosis and apoptosis suppression [ 107 ]. The outcomes and limitations of clinical and randomized clinical trials with adipose tissue grafting products are shown in Table  2 .

3 Conclusion

The last five years have witnessed a huge breakthrough in the translation of basic research and experimental studies of ADSCs into clinical practice. ADSCs are the most promising and easy-to-obtain cells when compared to other MSCs because of their satisfactory cultural, biological, and clinical properties. The future of ADSC-based therapies likely belongs to allogeneic ADSCs. ADSC-based treatment is a highly promising method that utilizes etiological treatment approaches for diseases that are accompanied by cell death or acute tissue loss such as diabetes mellitus type I, xerostomia, periodontitis, and wound treatment for them stem cell therapy. ADSCs act through their differentiation to the specific type of mature cells which are determined by the particular microenvironment or cell stimuli or via paracrine regulation, such as secretion of growth factors and cytokines.

The clinical translation of ADSCs requires proper validation in large controlled trials, discovery of the exact mechanism of action, research standardization, and the adoption of pre-determined therapeutic guidelines.

The vast majority of pre-clinical in vivo studies showed positive treatment outcomes, however there were only a few clinical trials performed, indicating that enough clinical evidence is not yet available to allow broad ADSCs implementation into clinical practice. Among the limiting factors are: small patient sample sizes, predominantly short-term observation time, a lack of adipose tissue graft standardization (procedure and cite of the graft harvesting, cell culturing protocols), deficit of clinical protocols and guidelines, and subjective scoring methods for clinical study results (such as visual assessment and patients’ response to pain) [ 22 ]. Currently, most preclinical studies and clinical trials reported that ADSCs are relatively safe and effective [ 104 , 115 ]. The issue of dose, quality of the graft and indications remains unresolved and debatable [ 62 ]. According to the reviewed literature analysis, adipose tissue-derived biological products such as (ADSCs, SFV, ADSCs-Ev) showed promising results in clinical and in vivo setting. However, one of the main limitations of ADSCs therapy, as all other biologics-based drugs, is a process of the graft standardization. Such standardization should take into consideration the functional properties of the graft, such as doubling time, specter and quantity of cytokines secretion, migration speed etc., all of which varied based on the procedure of their isolation, localization, and pretreatment used in order to provide predictable and effective treatment outcomes.

Data availability

Not applicable for review paper.

Availability of data and materials

Not applicable.

Abbreviations

• Adipose-derived stem cells

Mesenchymal stem cell

Bone marrow-derived stem cells

• Regenerative medicine

Visceral adipose tissue

White adipose tissue

Stromal vascular fraction

Extracellular vesicles

Vascular endothelial growth factor

Transforming growth factor

Matrix metalloproteinase

Tumor necrosis factor

Platelet-rich plasma

Interferon gamma

Peroxisome proliferator-activated receptor gamma

Nuclear factor kappa-light-chain-enhancer of activated B cells

Yang L, Hu Z-M, Jiang F-X, Wang W (2022) Stem cell therapy for insulin-dependent diabetes: Are we still on the road? WJSC 14:503–512. https://doi.org/10.4252/wjsc.v14.i7.503

Article   PubMed   PubMed Central   Google Scholar  

Cheng W, Zeng Y, Wang D (2022) Stem cell-based therapy for pulmonary fibrosis. Stem Cell Res Ther 13:492. https://doi.org/10.1186/s13287-022-03181-8

Article   CAS   PubMed   PubMed Central   Google Scholar  

Ma J, Lei P, Chen H et al (2022) Advances in lncRNAs from stem cell-derived exosome for the treatment of cardiovascular diseases. Front Pharmacol 13:986683. https://doi.org/10.3389/fphar.2022.986683

Hoang DM, Pham PT, Bach TQ et al (2022) Stem cell-based therapy for human diseases. Signal Transduct Target Ther 7:272. https://doi.org/10.1038/s41392-022-01134-4

Yan S, Campos de Souza S, Xie Z, Bao Y (2023) Research progress in clinical trials of stem cell therapy for stroke and neurodegenerative diseases. Ibrain 9:214–230. https://doi.org/10.1002/ibra.12095

El Sayed R, Shankar KM, Mankame AR, Cox CS Jr (2023) Innovations in cell therapy in pediatric diseases: a narrative review. Transl Pediatr 12:1239–1257. https://doi.org/10.21037/tp-23-92

Orozco-Solares TE, León-Moreno LC, Rojas-Rizo A et al (2022) Allogeneic mesenchymal stem cell-based treatment legislation in Latin America: the need for standardization in a medical tourism context. Stem Cells Dev 31:143–162. https://doi.org/10.1089/scd.2022.0013

Article   CAS   PubMed   Google Scholar  

https://www.Fda.Gov/Vaccines-Blood-Biologics/Cellular-Gene-Therapy-Products/Approved-Cellular-and-Gene-Therapy-Products .

Glenn Cohen I, Simana S (2018) Regulation of stem cell therapy travel. Curr Stem Cell Rep 4:220–227. https://doi.org/10.1007/s40778-018-0134-8

Article   Google Scholar  

Şovrea AS, Boşca AB, Constantin AM et al (2019) State of the art in human adipose stem cells and their role in therapy. Rom J Morphol Embryol 60:7–31

PubMed   Google Scholar  

Frese L, Dijkman PE, Hoerstrup SP (2016) Adipose tissue-derived stem cells in regenerative medicine. Transfus Med Hemother 43:268–274. https://doi.org/10.1159/000448180

Youn GM, Woodall BM, Elena N et al (2018) Arthroscopic bone marrow aspirate concentrate harvesting from the intercondylar notch of the knee. Arthrosc Tech 7:e1173–e1176. https://doi.org/10.1016/j.eats.2018.07.016

Pittenger MF, Mackay AM, Beck SC et al (1979) (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147. https://doi.org/10.1126/science.284.5411.143

Sivasubramaniyan K, Ilas DC, Harichandan A et al (2018) Bone marrow-harvesting technique influences functional heterogeneity of mesenchymal stem/stromal cells and cartilage regeneration. Am J Sports Med 46:3521–3531. https://doi.org/10.1177/0363546518804807

Tanasale B, Kits J, Kluin PM et al (2013) Pain and anxiety during bone marrow biopsy. Pain Manag Nurs 14:310–317. https://doi.org/10.1016/j.pmn.2011.06.007

Article   PubMed   Google Scholar  

Filbet M, Fawoubo A, Tricou C et al (2020) Management of the procedural pain induced by bone marrow biopsies: an observational study. Ann Clin Oncol. https://doi.org/10.31487/j.ACO.2020.01.06

Mazini L, Rochette L, Amine M, Malka G (2019) Regenerative capacity of adipose derived stem cells (ADSCs), comparison with mesenchymal stem cells (MSCs). IJMS 20:2523. https://doi.org/10.3390/ijms20102523

Bourin P, Bunnell BA, Casteilla L et al (2013) Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 15:641–648. https://doi.org/10.1016/j.jcyt.2013.02.006

Macrin D, Joseph JP, Pillai AA, Devi A (2017) Eminent sources of adult mesenchymal stem cells and their therapeutic imminence. Stem Cell Rev and Rep 13:741–756. https://doi.org/10.1007/s12015-017-9759-8

Hass R, Kasper C, Böhm S, Jacobs R (2011) Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal 9:12. https://doi.org/10.1186/1478-811X-9-12

Sanchez-Petitto G, Rezvani K, Daher M et al (2023) Umbilical cord blood transplantation: connecting its origin to its future. Stem Cells Transl Med. https://doi.org/10.1093/stcltm/szac086

Malhotra A, Thebaud B, Paton MCB et al (2023) Advances in neonatal cell therapies: proceedings of the First Neonatal Cell Therapies Symposium (2022). Pediatr Res 94:1631–1638. https://doi.org/10.1038/s41390-023-02707-x

Zhang J, Huang X, Wang H et al (2015) The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy. Stem Cell Res Ther 6:234. https://doi.org/10.1186/s13287-015-0240-9

Ankrum JA, Ong JF, Karp JM (2014) Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol 32:252–260. https://doi.org/10.1038/nbt.2816

Biniazan F, Stoian A, Haykal S (2024) Adipose-derived stem cells: angiogenetic potential and utility in tissue engineering. Int J Mol Sci 25:2356. https://doi.org/10.3390/ijms25042356

Nasser RA, Arya SS, Alshehhi KH et al (2024) Conducting polymer scaffolds: a new frontier in bioelectronics and bioengineering. Trends Biotechnol. https://doi.org/10.1016/j.tibtech.2023.11.017

Zuk PA, Zhu M, Mizuno H et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228. https://doi.org/10.1089/107632701300062859

Madhavan AA, Summerfield D, Hunt CH et al (2020) Polyclonal lymphocytic infiltrate with arachnoiditis resulting from intrathecal stem cell transplantation. Neuroradiol J 33:174–178. https://doi.org/10.1177/1971400920902451

Lyons S, Salgaonkar S, Flaherty GT (2022) International stem cell tourism: a critical literature review and evidence-based recommendations. Int Health 14:132–141. https://doi.org/10.1093/inthealth/ihab050

Tobita M, Konomi K, Torashima Y et al (2016) Japan’s challenges of translational regenerative medicine: Act on the safety of regenerative medicine. Regen Ther 4:78–81. https://doi.org/10.1016/j.reth.2016.04.001

Connolly R, O’Brien T, Flaherty G (2014) Stem cell tourism–a web-based analysis of clinical services available to international travellers. Travel Med Infect Dis 12:695–701. https://doi.org/10.1016/j.tmaid.2014.09.008

Rehfeld A, Nylander M, Karnov K (2017) Adipose tissue. Compendium of histology. Springer International Publishing, Cham, pp 201–207

Chapter   Google Scholar  

Mescher AL, Junqueira LCU (2013) Junqueira’s basic histology: text and atlas, 13th edn. McGraw-Hill Medical, New York, NY

Google Scholar  

Ibrahim MM (2010) Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev 11:11–18. https://doi.org/10.1111/j.1467-789X.2009.00623.x

Shinde AB, Song A, Wang QA (2021) Brown adipose tissue heterogeneity, energy metabolism, and beyond. Front Endocrinol 12:651763. https://doi.org/10.3389/fendo.2021.651763

Tordjman J (2013) Histology of adipose tissue. In: Bastard J-P, Fève B (eds) Physiology and physiopathology of adipose tissue. Springer Paris, Paris, pp 67–75

Blaszkiewicz M, Willows JW, Johnson CP, Townsend KL (2019) The importance of peripheral nerves in adipose tissue for the regulation of energy balance. Biology (Basel) 8:10. https://doi.org/10.3390/biology8010010

Beregova TV, Neporada KS, Skrypnyk M et al (2017) Efficacy of nanoceria for periodontal tissues alteration in glutamate-induced obese rats-Multidisciplinary considerations for personalized dentistry and prevention. EPMA J. https://doi.org/10.1007/s13167-017-0085-7

González-Muniesa P, Mártinez-González M-A, Hu FB et al (2017) Obesity. Nat Rev Dis Primers 3:17034. https://doi.org/10.1038/nrdp.2017.34

Nguyen A, Guo J, Banyard DA et al (2016) Stromal vascular fraction: a regenerative reality? Part 1: current concepts and review of the literature. J Plast Reconstr Aesthet Surg 69:170–179. https://doi.org/10.1016/j.bjps.2015.10.015

Ramakrishnan VM, Boyd NL (2018) The adipose stromal vascular fraction as a complex cellular source for tissue engineering applications. Tissue Eng Part B Rev 24:289–299. https://doi.org/10.1089/ten.teb.2017.0061

Zhu Y, Liu T, Song K et al (2008) Adipose-derived stem cell: a better stem cell than BMSC. Cell Res 18:S165–S165. https://doi.org/10.1038/cr.2008.255

Cieśla J, Tomsia M (2021) Cadaveric stem cells: their research potential and limitations. Front Genet 12:798161. https://doi.org/10.3389/fgene.2021.798161

Rao P, Deo D, Marchioni M et al (2019) 24: deceased donor adipose tissue: an untapped source of mesenchymal stem cells. Transplantation 103:S5–S6. https://doi.org/10.1097/01.tp.0000581296.60427.ad

Kim SM, Lun M, Wang M et al (2014) Loss of white adipose hyperplastic potential is associated with enhanced susceptibility to insulin resistance. Cell Metab 20:1049–1058. https://doi.org/10.1016/j.cmet.2014.10.010

Skrypnyk M, Petrushanko T, Neporada K et al (2022) Colonization resistanCe of oral muCosa in individuals with diverse body mass index. J Stomatol. https://doi.org/10.5114/jos.2022.119168

Skrypnyk M, Petrushanko T, Neporada K et al (2022) Dependence of the dental status of young individuals with different body weights on their eating behavior. Acta Facult Med Naissensis. https://doi.org/10.5937/afmnai39-35901

Wada Y, Ikemoto T, Morine Y et al (2019) The differences in the characteristics of insulin-producing cells using human adipose-tissue derived mesenchymal stem cells from subcutaneous and visceral tissues. Sci Rep 9:13204. https://doi.org/10.1038/s41598-019-49701-0

Yoon H-J, Jung Ho W (2019) Minimum criteria for adipose derived stem cells. Clin Med Rep. https://doi.org/10.15761/CMR.1000145

Hong S, van Kaer L (1999) Immune privilege: keeping an eye on natural killer T cells. J Exp Med 190:1197–1200. https://doi.org/10.1084/jem.190.9.1197

Zangi L, Margalit R, Reich-Zeliger S et al (2009) Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells. Stem Cells 27:2865–2874. https://doi.org/10.1002/stem.217

Mazini L, Rochette L, Admou B et al (2020) Hopes and limits of adipose-derived stem cells (ADSCs) and mesenchymal stem cells (MSCs) in wound healing. IJMS 21:1306. https://doi.org/10.3390/ijms21041306

Ren M-L, Peng W, Yang Z-L et al (2012) Allogeneic adipose-derived stem cells with low immunogenicity constructing tissue-engineered bone for repairing bone defects in pigs. Cell Transplant 21:2711–2721. https://doi.org/10.3727/096368912X654966

Gentile P, Sterodimas A (2020) Adipose stem cells (ASCs) and stromal vascular fraction (SVF) as a potential therapy in combating (COVID-19)-disease. Aging Dis 11:465. https://doi.org/10.14336/AD.2020.0422

Copcu HE (2020) Potential using of fat-derived stromal cells in the treatment of active disease, and also, in both pre- and post-periods in COVID-19. Aging Dis 11:730. https://doi.org/10.14336/AD.2020.0621

Cypess AM, Weiner LS, Roberts-Toler C et al (2015) Activation of human brown adipose tissue by a β3-adrenergic receptor agonist. Cell Metab 21:33–38. https://doi.org/10.1016/j.cmet.2014.12.009

Liu X, Zheng Z, Zhu X et al (2013) Brown adipose tissue transplantation improves whole-body energy metabolism. Cell Res 23:851–854. https://doi.org/10.1038/cr.2013.64

Khazaei S, Keshavarz G, Bozorgi A et al (2022) Adipose tissue-derived stem cells: a comparative review on isolation, culture, and differentiation methods. Cell Tissue Bank 23:1–16. https://doi.org/10.1007/s10561-021-09905-z

Si Z, Wang X, Sun C et al (2019) Adipose-derived stem cells: sources, potency, and implications for regenerative therapies. Biomed Pharmacother 114:108765. https://doi.org/10.1016/j.biopha.2019.108765

Tsuji W (2014) Adipose-derived stem cells: Implications in tissue regeneration. WJSC 6:312. https://doi.org/10.4252/wjsc.v6.i3.312

Shao X, Ai G, Wang L et al (2019) Adipose-derived stem cells transplantation improves endometrial injury repair. Zygote 27:367–374. https://doi.org/10.1017/S096719941900042X

Mazini L, Ezzoubi M, Malka G (2021) Overview of current adipose-derived stem cell (ADSCs) processing involved in therapeutic advancements: flow chart and regulation updates before and after COVID-19. Stem Cell Res Ther 12:1. https://doi.org/10.1186/s13287-020-02006-w

Raposio E, Simonacci F, Perrotta RE (2017) Adipose-derived stem cells: Comparison between two methods of isolation for clinical applications. Ann Med Surg (Lond) 20:87–91. https://doi.org/10.1016/j.amsu.2017.07.018

Dalerba P, Diehn M, Weissman IL, Clarke MF (2020) Stem Cells, Cell Differentiation, and Cancer. In: Abeloff’s Clinical Oncology. Elsevier, pp 97–107.e5

Xin L, Lin X, Pan Y et al (2019) A collagen scaffold loaded with human umbilical cord-derived mesenchymal stem cells facilitates endometrial regeneration and restores fertility. Acta Biomater 92:160–171. https://doi.org/10.1016/j.actbio.2019.05.012

Wong DE, Banyard DA, Santos PJF et al (2019) Adipose-derived stem cell extracellular vesicles: a systematic review✰. J Plast Reconstr Aesthet Surg 72:1207–1218. https://doi.org/10.1016/j.bjps.2019.03.008

Bazzan E, Tinè M, Casara A et al (2021) Critical review of the evolution of extracellular vesicles’ knowledge: from 1946 to today. Int J Mol Sci 22:6417. https://doi.org/10.3390/ijms22126417

Gokce A, Abd Elmageed ZY, Lasker GF et al (2014) Adipose tissue-derived stem cell therapy for prevention and treatment of erectile dysfunction in a rat model of Peyronie’s disease. Andrology 2:244–251. https://doi.org/10.1111/j.2047-2927.2013.00181.x

Braga Osorio Gomes Salgado JA, Goncalves Reis LR, Jorge Carvalho Sousa N, et al (2010) Adipose Tissue Derived Stem Cells Secretome: Soluble Factors and Their Roles in Regenerative Medicine. CSCR 5:103–110. https://doi.org/10.2174/157488810791268564

Hu X, Pan J, Li Y et al (2022) Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion. Stem Cell Res Ther 13:21. https://doi.org/10.1186/s13287-021-02668-0

el Bassit G, Patel RS, Carter G et al (2016) MALAT1 in human adipose stem cells modulates survival and alternative splicing of PKCδII in HT22 cells. Endocrinology. https://doi.org/10.1210/en.2016-1819

Article   PubMed Central   Google Scholar  

Patel NA, Moss LD, Lee J-Y et al (2018) Long noncoding RNA MALAT1 in exosomes drives regenerative function and modulates inflammation-linked networks following traumatic brain injury. J Neuroinflammation 15:204. https://doi.org/10.1186/s12974-018-1240-3

Bonafede R, Scambi I, Peroni D et al (2016) Exosome derived from murine adipose-derived stromal cells: neuroprotective effect on in vitro model of amyotrophic lateral sclerosis. Exp Cell Res 340:150–158. https://doi.org/10.1016/j.yexcr.2015.12.009

Zhao S, Qi W, Zheng J et al (2020) Exosomes derived from adipose mesenchymal stem cells restore functional endometrium in a rat model of intrauterine adhesions. Reprod Sci 27:1266–1275. https://doi.org/10.1007/s43032-019-00112-6

Ma L, Wei J, Zeng Y et al (2022) Mesenchymal stem cell-originated exosomal circDIDO1 suppresses hepatic stellate cell activation by miR-141-3p/PTEN/AKT pathway in human liver fibrosis. Drug Deliv 29:440–453. https://doi.org/10.1080/10717544.2022.2030428

Zhang Z, Shang J, Yang Q et al (2023) Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism. J Nanobiotechnol 21:29. https://doi.org/10.1186/s12951-023-01788-4

Article   CAS   Google Scholar  

Qu Y, Zhang Q, Cai X et al (2017) Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation. J Cell Mol Med 21:2491–2502. https://doi.org/10.1111/jcmm.13170

Chen F, Zhang H, Wang Z et al (2017) Adipose-derived stem cell-derived exosomes ameliorate erectile dysfunction in a rat model of type 2 diabetes. J Sex Med 14:1084–1094. https://doi.org/10.1016/j.jsxm.2017.07.005

Zhu LL, Huang X, Yu W et al (2018) Transplantation of adipose tissue-derived stem cell-derived exosomes ameliorates erectile function in diabetic rats. Andrologia 50:e12871. https://doi.org/10.1111/and.12871

Zhang Y, Zouboulis CC, Xiao Z (2024) Exosomes from adipose-derived stem cells activate sebocytes through the PI3K/AKT/SREBP-1 pathway to accelerate wound healing. Cell Tissue Res. https://doi.org/10.1007/s00441-024-03872-z

Santos J, Dalla P (2021) A molecular analysis of cytokine content across extracellular vesicles, secretions, and intracellular space from different site-specific adipose-derived stem cells. IJMS 23:397. https://doi.org/10.3390/ijms23010397

Alicka M, Major P, Wysocki M, Marycz K (2019) Adipose-derived mesenchymal stem cells isolated from patients with type 2 diabetes show reduced “stemness” through an altered secretome profile, impaired anti-oxidative protection, and mitochondrial dynamics deterioration. JCM 8:765. https://doi.org/10.3390/jcm8060765

Tobita M, Uysal CA, Guo X et al (2013) Periodontal tissue regeneration by combined implantation of adipose tissue-derived stem cells and platelet-rich plasma in a canine model. Cytotherapy 15:1517–1526. https://doi.org/10.1016/j.jcyt.2013.05.007

Tobita M, Uysal AC, Ogawa R et al (2008) Periodontal tissue regeneration with adipose-derived stem cells. Tissue Eng Part A 14:945–953. https://doi.org/10.1089/ten.tea.2007.0048

Wang L, Lu Y, Cai G et al (2022) Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif. Front Physiol 13:917510. https://doi.org/10.3389/fphys.2022.917510

Louis F, Sowa Y, Irie S, Higuchi Y, Kitano S, Mazda O, Matsusaki M (2022) Injectable prevascularized mature adipose tissues (iPAT) to achieve long-term sur-vival in soft tissue regeneration. Adv Healthcare Mater. https://doi.org/10.1002/adhm.202201440

Li W, Yang Y, Lin Y, Mu D (2024) In vitro study of thymosin beta 4 promoting transplanted fat survival by regulating adipose-derived stem cells. Aesthetic Plast Surg. https://doi.org/10.1007/s00266-024-03861-1

Demir M, Yılmaz EM, İpek E et al (2022) Effects of adipose tissue-derived mesenchymal stem cells and/or sildenafil citrate in experimental colon anastomosis model. Ulus Travma Acil Cerrahi Derg 28:1373–1381. https://doi.org/10.14744/tjtes.2021.57500

Kim JH, Kim TY, Goo B, Park Y (2024) Bee venom stimulates growth factor release from adipose-derived stem cells to promote hair growth. Toxins (Basel) 16:84. https://doi.org/10.3390/toxins16020084

Tynecka M, Janucik A, Niemira M et al (2022) The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung. Front Immunol 13:967487. https://doi.org/10.3389/fimmu.2022.967487

Kangari P, Roshangar L, Iraji A et al (2022) Accelerating effect of Shilajit on osteogenic property of adipose-derived mesenchymal stem cells (ASCs). J Orthop Surg Res 17:424. https://doi.org/10.1186/s13018-022-03305-z

Felthaus O, Vedlin S, Eigenberger A et al (2024) Exosomes from adipose-tissue-derived stem cells induce proapoptotic gene expression in breast tumor cell line. Int J Mol Sci 25:2190. https://doi.org/10.3390/ijms25042190

Lappin T, Cheng T (2021) An urgent need for standardization of stem cells and stem cell-derived products toward clinical applications. Stem Cells Transl Med 10:S1–S3. https://doi.org/10.1002/sctm.21-0269

Tragoonlugkana P, Chitchongyingcharoen N, Pruksapong C et al (2024) The use of human platelet lysate as a coating substance for adipose-derived stem cell expansion. Front Biosci Landmark 29:88. https://doi.org/10.31083/j.fbl2902088

Greenwood V, Clausen P, Matuska AM (2022) Micro-fragmented adipose tissue cellular composition varies by processing device and analytical method. Sci Rep 12:16107. https://doi.org/10.1038/s41598-022-20581-1

Taha S, Akova E, Saller MM et al (2022) Early transcriptional changes of adipose-derived stem cells (ADSCs) in cell culture. Medicina (B Aires) 58:1249. https://doi.org/10.3390/medicina58091249

Schipper BM, Marra KG, Zhang W et al (2008) Regional anatomic and age effects on cell function of human adipose-derived stem cells. Ann Plast Surg 60:538–544. https://doi.org/10.1097/SAP.0b013e3181723bbe

Aksu AE, Rubin JP, Dudas JR, Marra KG (2008) Role of gender and anatomical region on induction of osteogenic differentiation of human adipose-derived stem cells. Ann Plast Surg 60:306–322. https://doi.org/10.1097/SAP.0b013e3180621ff0

van Harmelen V, Skurk T, Röhrig K et al (2003) Effect of BMI and age on adipose tissue cellularity and differentiation capacity in women. Int J Obes Relat Metab Disord 27:889–895. https://doi.org/10.1038/sj.ijo.0802314

Ryu Y, Ha H, Lee C et al (2016) ADSC from younger donors have more abundant initial ADSC yield. Cytotherapy 18:S79. https://doi.org/10.1016/j.jcyt.2016.03.164

Abbo O, Taurand M, Monsarrat P et al (2017) Comparison between pediatric and adult adipose mesenchymal stromal cells. Cytotherapy 19:395–407. https://doi.org/10.1016/j.jcyt.2016.11.012

Ock S-A, Lee Y-M, Park J-S et al (2016) Evaluation of phenotypic, functional and molecular characteristics of porcine mesenchymal stromal/stem cells depending on donor age, gender and tissue source. J Vet Med Sci 78:987–995. https://doi.org/10.1292/jvms.15-0596

Altamirano-Samaniego F, Enciso-Benavides J, Rojas N et al (2022) First report of canine morbillivirus infection of adipose tissue-derived stem cells from dogs with distemper. Vet World. https://doi.org/10.14202/vetworld.2022.1835-1842

Firriolo JM, Condé-Green A, Pu LLQ (2022) Fat grafting as regenerative surgery: a current review. Plast Reconstr Surg 150:1340e–1347e. https://doi.org/10.1097/PRS.0000000000009710

Shetty AK (2020) Mesenchymal stem cell infusion shows promise for combating coronavirus (COVID-19)- induced pneumonia. Aging Dis 11:462–464. https://doi.org/10.14336/AD.2020.0301

Alcayaga-Miranda F, Cuenca J, Khoury M (2017) Antimicrobial activity of mesenchymal stem cells: current status and new perspectives of antimicrobial peptide-based therapies. Front Immunol 8:339. https://doi.org/10.3389/fimmu.2017.00339

Al-Ghadban S, Bunnell BA (2020) Adipose tissue-derived stem cells: immunomodulatory effects and therapeutic potential. Physiology 35:125–133. https://doi.org/10.1152/physiol.00021.2019

Zhou L, Wang H, Yao S et al (2022) Efficacy of human adipose derived mesenchymal stem cells in promoting skin wound healing. J Healthc Eng 2022:6590025. https://doi.org/10.1155/2022/6590025

Randelli PS, Cucchi D, Fossati C et al (2022) Arthroscopic rotator cuff repair augmentation with autologous microfragmented lipoaspirate tissue is safe and effectively improves short-term clinical and functional results: a prospective randomized controlled trial with 24-month follow-up. Am J Sports Med 50:1344–1357. https://doi.org/10.1177/03635465221083324

el Zarif M et al (2020) Corneal stroma cell density evolution in keratoconus corneas following the implantation of adipose mesenchymal stem cells and corneal laminas: an in vivo confocal microscopy study. Investigative Opthalmology & Visual Science 61:22. https://doi.org/10.1167/iovs.61.4.22

Zheng C, Chiu I, Chen Y et al (2022) Allogeneic adipose tissue-derived stem cells ELIXCYTE ® in chronic kidney disease: a phase I study assessing safety and clinical feasibility. J Cell Mol Med 26:2972–2980. https://doi.org/10.1111/jcmm.17310

Ferracini R, Alessio-Mazzola M, Sonzogni B et al (2022) Age and synovitis affect the results of the treatment of knee osteoarthritis with microfragmented autologous fat tissue. Knee Surg Sports Traumatol Arthrosc. https://doi.org/10.1007/s00167-022-07139-4

Behrangi E, Moradi S, Ghassemi M et al (2022) The investigation of the efficacy and safety of stromal vascular fraction in the treatment of nanofat-treated acne scar: a randomized blinded controlled clinical trial. Stem Cell Res Ther 13:298. https://doi.org/10.1186/s13287-022-02957-2

Lynggaard CD, Grønhøj C, Jensen SB et al (2022) Long-term safety of treatment with autologous mesenchymal stem cells in patients with radiation-induced xerostomia: primary results of the MESRIX phase I/II randomized trial. Clin Cancer Res 28:2890–2897. https://doi.org/10.1158/1078-0432.CCR-21-4520

Ceccarelli S, Pontecorvi P, Anastasiadou E et al (2020) Immunomodulatory effect of adipose-derived stem cells: the cutting edge of clinical application. Front Cell Dev Biol. https://doi.org/10.3389/fcell.2020.00236

Download references

Acknowledgements

The author thank Dr. Darren Smith for kindly providing editorial assistance while preparing the manuscript.

Author information

Authors and affiliations.

Department: Centre for Health Informatics, Australian Institute of Health Innovation, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia

Maksym Skrypnyk

You can also search for this author in PubMed   Google Scholar

Contributions

Corresponding author.

Correspondence to Maksym Skrypnyk .

Ethics declarations

Conflict of interest.

The corresponding author states that there is no conflict of interest.

Ethics approval and consent to participate

Consent for publication, additional information, publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Skrypnyk, M. Current progress and limitations of research regarding the therapeutic use of adipose-derived stem cells: literature review. J.Umm Al-Qura Univ. Appll. Sci. (2024). https://doi.org/10.1007/s43994-024-00147-9

Download citation

Received : 06 December 2023

Accepted : 26 March 2024

Published : 17 April 2024

DOI : https://doi.org/10.1007/s43994-024-00147-9

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Cell therapy
• Mesenchymal stem cells
• Adipose tissue
• Find a journal
• Publish with us
• Track your research

SYSTEMATIC REVIEW article

Facebook reactions in the context of politics and social issues: a systematic literature review provisionally accepted.

• 1 University of Urbino Carlo Bo, Italy

The final, formatted version of the article will be published soon.

In February 2016, Facebook launched five "Reactions" (i.e., Love, Haha, Wow, Sad, and anger) for users to emote their experiences with the posts, which were an extension of the "Like" button and were edited versions of Unicode emojis. Scholars used them to investigate user behavior and situation-based current topics to measure various aspects of socioeconomic and psychological topics. This literature review focuses on "Facebook reactions," examines the literature, and serves as a comprehensive and cumulative approach, summarizing the existing literature and research articles, scattered under different names. However, to get comparable results within broader classification and themes, we seek how "Facebook reactions" play a role in different or comparable topics and their results.Articles were collected using Google Scholar and other search engines. We used the keywords "Facebook" and "Reaction," with a combination of different key phrases and Boolean operators. Seventy-three articles are taken into consideration from 2016-2023. Matrix and Reference lists were scanned with different topics classified date-wise. The articles cover a wide range of topics/information such as Political News, Far-right and Extremist Parties, Racism, and Hate speech with COVID-19. Our Findings reveal nuanced patterns of the reaction distribution based on the topics. The positive reaction dominates articles related to lifestyle and entertainment, while the articles addressing sociopolitical issues elicit a wider range of reactions, including negative sentiments. Moreover, we observe that emotional content tends to get higher reaction volumes regardless of sentiment.

Keywords: facebook, Reactions, emotion, Emoji, Politics, Social issue

Received: 30 Jan 2024; Accepted: 16 Apr 2024.

Copyright: © 2024 Anwar and Giglietto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mr. Sawood Anwar, University of Urbino Carlo Bo, Urbino, Italy

People also looked at

Help | Advanced Search

Computer Science > Computation and Language

Title: related work and citation text generation: a survey.

Abstract: To convince readers of the novelty of their research paper, authors must perform a literature review and compose a coherent story that connects and relates prior works to the current work. This challenging nature of literature review writing makes automatic related work generation (RWG) academically and computationally interesting, and also makes it an excellent test bed for examining the capability of SOTA natural language processing (NLP) models. Since the initial proposal of the RWG task, its popularity has waxed and waned, following the capabilities of mainstream NLP approaches. In this work, we survey the zoo of RWG historical works, summarizing the key approaches and task definitions and discussing the ongoing challenges of RWG.

Submission history

Access paper:.

• HTML (experimental)
• Other Formats

References & Citations

• Google Scholar
• Semantic Scholar

BibTeX formatted citation

Bibliographic and Citation Tools

Code, data and media associated with this article, recommenders and search tools.

• Institution

arXivLabs: experimental projects with community collaborators

arXivLabs is a framework that allows collaborators to develop and share new arXiv features directly on our website.

Both individuals and organizations that work with arXivLabs have embraced and accepted our values of openness, community, excellence, and user data privacy. arXiv is committed to these values and only works with partners that adhere to them.

Have an idea for a project that will add value for arXiv's community? Learn more about arXivLabs .