Mapping global trends in adipose-derived mesenchymal stem cell research: A bibliometric analysis using scopus database

Background and objective Adipose-derived mesenchymal stem cells (AdMSC) are multipotent adult mesenchymal cells isolated and cultured from the stromal vascular fraction derived from adipose tissue. The present study was conducted to analyze the global trends in AdMSC research using bibliometric and visual analysis tools. Methods The literature search was done on February 13, 2022, using appropriate keywords and inclusion-exclusion criteria from the Scopus database. The extracted data were retrospectively analyzed and visualized using Bibliometrics and R packages and VOSviewer. Results Preliminary analysis identified 1569 documents from the Scopus database published between 2005 and 2021. The average citations received per document was 26.51, whereas the average citations per year per document was 3.347. In addition, the selected documents had an h-index value of 90. China was the most productive country, whereas Seoul National University (South Korea) was identified as the most productive institute/university in AdMSC research. In addition, the National Natural Science Foundation of China funded the most research studies in AdMSC research. Conclusion The findings from this study indicate a progressive increase in interest among the research community towards AdMSC, suggesting promising prospects in the coming years.


Introduction
Stem cells play a major role in different cell-based and cell-free therapeutic strategies [1][2][3]. They are isolated and cultured from several sources. Bone marrow and adipose tissue are the two important sources of mesenchymal stem cells (MSC) [4]. Adipose-derived mesenchymal stem cells (AdMSC) are multipotent adult mesenchymal cells isolated and cultured from the stromal vascular fraction derived from adipose tissue [5]. They can differentiate into several cell lineages such as adipocytes, chondrocytes, cardiomyocytes, hepatocytes, osteoblasts, vascular endothelial cells, pancreatic cells, and neural cells [6]. AdMSC is gaining importance in regenerative medicine due to the higher yield of MSCs (100-1000 times) compared to bone marrow-derived mesenchymal stem cells (BM-MSC) [7]. In addition, adipose tissue can be harvested easily by minimally invasive surgical techniques, processed by enzymatic or non-enzymatic methods, and isolated and cultured to obtain AdMSC [5,8].
AdMSC has therapeutic applications in musculoskeletal pathologies such as osteochondral focal defects, knee, and hip osteoarthritis, rotator cuff, and Achilles tendinopathies [8]. In addition, they are also evaluated for utility in wound repair, renal repair, hepatic repair, myocardial repair, neuroprotection, neurotrophic effects, and other regenerative medicine applications [9]. Over the past decade, there has been a rapid increase in the publications as well as several novel concepts and advancements in the field of AdMSC research [10]. Therefore, a systematic assessment of research has to be conducted to evaluate the progress of science towards research on AdMSC.
Bibliometric analysis is a systematic method used to collect and analyze large volumes of scientific data. It helps to identify the ongoing trends in a specific field while providing a glance at the emerging areas in that field [11]. In addition, the bibliometric analysis also helps to understand the emerging trends in publication patterns, journal performance, and collaboration patterns [11]. Scopus is the multidisciplinary database developed by Elsevier and first launched in November 2004 [12]. It is an ideal database that is better suited for analyzing research results. In addition, Scopus has more inclusive content coverage than Web of Science (Clarivate), making it more convenient for bibliometric analysis [12].
The present study was conducted to analyze the global trends in AdMSC research within the Scopus database using bibliometric and visualization tools. Furthermore, the study was designed in such a way as to gain a better understanding of the present scenario in stem cell research by analyzing different characteristics.

Search strategy and data collection
The literature search and data collection was done on February 13, 2022, from the Scopus database (available at: https://www.scopus.com /home.uri). The search was limited to journal articles published in the English language till 2021. Therefore, we excluded all publications such as reviews, editorials, book chapters, books, conference papers, letters, notes, short surveys, erratum, reports, and retracted papers. In addition, all journal articles published in other languages were also excluded. The following search strategy was used for data collection from the Scopus database: TITLE ("adipose-derived mesenchymal stem cell" OR "adipose derived mesenchymal stem cell" OR "adipose tissue-derived mesenchymal stem cell" OR "adipose tissue derived mesenchymal stem cell") AND (LIMIT-TO (SRCTYPE, "j")) AND (LIMIT-TO (DOCTYPE, "ar")) AND (LIMIT-TO (LANGUAGE, "English")) AND (EXCLUDE (PUBYEAR, 2022)).

Analysis of variables
The data was extracted from the selected articles in terms of the following variables: articles published each year, top ten authors, institutes, countries, and journals having the highest number of published articles, top ten funding agencies, and top ten most cited articles related to AdMSC research. In addition, the 2021 Journal Impact Factor™ (JIF) of the top ten journals was extracted from the Journal Citation Reports™ (JCR). The metadata was analyzed using the R studio and bibliometrix package for the R statistical programming language as a unique opensource tool designed for performing comprehensive science mapping analysis [13].

Visualization
The extracted data were visualized using the network visualization software VOSviewer (https://www.vosviewer.com) [14]. The software was used for the graphical representation of bibliometric maps.

Scopus database output
The initial search identified 1747 documents in the Scopus database published between 2005 and 2021. However, after refining the search protocol based on inclusion and exclusion criteria, 1569 articles from 618 sources were selected for further analysis and data extraction (Fig. 1). The Scopus database categorized these 1569 articles into 25 subject areas. Among these, the top 10 subject areas in AdMSC research are biochemistry, genetics and molecular biology 906 (33.6%), medicine 669 (24.8%), engineering 174 (6.4%), chemical engineering 133 (4.9%), materials science 131 (4.9%), immunology and microbiology 119 (4.4%), pharmacology, toxicology and pharmaceutics 98 (3.6%), veterinary 80 (3.0%), and multidisciplinary 78 (2.9%) (Fig. 2a). The average citations received per document were 26.51, whereas the average citations per year per document were 3.347 (Table 1). In addition, the articles had an h-index value of 90. The h-index is calculated based on the highest number of papers included that have had at least the same number of citations.

Time trend of publications
The annual global trend in total publications is shown in Fig. 2b. A steady increase in the publications was observed between 2005 and 2021, with a peak in 2021. This indicates that AdMSC research is rapidly gaining importance in the research community. Among the 1569 articles extracted from the Scopus database, 212 were published in 2021. The total citations received increased from 2005 to 2021. In addition, the average mean of total citation per year (MeanTCperYear) during the year 2005-2021 on adipose-derived mesenchymal stem cell research is plotted in Fig. 2b.

Most productive institutes and countries involved in AdMSC research
The top ten productive institutes/universities and countries publishing (based on total publications) on AdMSC research were identified. Among the 1569 articles evaluated, the corresponding authors of 410 publications originated from China, followed by South Korea (232) and Iran (141) ( Table 2). Other productive countries included the United States (104), Japan (77), Spain (57), Italy (55), Germany (47), Turkey (40), and Brazil (34). Among the countries, China has a robust national collaboration in AdMSC research with 361 single-country publications (indicative of intra-country collaboration) and 49 multiple-country publications (indicative of inter-country collaboration). However, the top ten listed countries involved in AdMSC research have a low Multiple Country Publications ratio (MCP Ratio less than 0.50), indicating lower  (21), National Sun Yat-Sen University (20), and Asia University (20) (Fig. 3).

Top ten authors involved in AdMSC research
Among the 7056 authors identified, the characteristics of the top ten productive individuals are given in Table 3. These prolific authors included Wang Y.

Top ten journals publishing AdMSC research
Among the 1569 articles evaluated in this study, 50 articles were published in Stem Cell Research and Therapy (3.19%), followed by 40 articles in Plos One (2.55%), and 33 articles in Stem Cells and Development (2.10%). The other important journals include Stem Cells International (33, 2.10%), International Journal of Molecular Sciences   Table 4). The publication pattern of the top ten journals is illustrated in Fig. 4. Among the top ten journals, Stem Cell Research and Therapy journal has the highest Journal Impact Factor™ (Journal Citation Reports -Clarivate Analytics).

Top ten most cited articles in AdMSC research
The characteristics of the top ten most cited articles on AdMSC research are given in Table 5. None of the journals that published the top ten articles have more than one article. Furthermore, the In addition, the oldest article within the top ten most-cited article was published in the year 2005, while the most recent one was in 2016. The top ten publications contributed 4324 citations to the total citation count. The top-cited article on AdMSC research was published in Stem Cells journal titled "Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease." The study evaluated the immunoregulatory properties of human and mouse-derived AdMSC. It provided the first experimental proof that AdMSC can control graft-versus-host disease associated with allogeneic hematopoietic transplantation [15].  (17), and Ministry of Science, ICT, and Future Planning (16) (Fig. 5).

Network visualization map
Co-author analysis helps to establish the relationship between authors, organizations, and countries based on total link strength. The network indicating the relationship between authors, organizations, and countries is visualized and presented in Fig. 6. The network visualization map illustrating the relationship between authors was plotted among individuals with a minimum of 15 documents. Similarly, organizations with a minimum of three documents and countries with a minimum of five were selected based on the links and total link strength. The size of the circle indicates the total published articles (larger the circle, more the published articles). In contrast, line width indicates the link strength (wider line indicates more link strength). The distance between two Table 2 Top ten corresponding author's countries and most cited countries publishing on adipose-derived mesenchymal stem cell research.

Table 3
The characteristics of top ten most productive authors over time publishing on adipose-derived mesenchymal stem cell research. circles indicates the relatedness of the nodes.

Discussion
AdMSC is gaining importance in plastic and reconstructive surgery due to its therapeutic applications in fat grafting, facial rejuvenation, scleroderma, and wound healing [16]. The therapeutic potential of AdMSC is mediated by secretory products such as cytokines, growth factors, extracellular vesicles, and proteins [17]. MSCs derived secretomes are gaining importance in ongoing studies since they eliminate the disadvantages of cell-based therapy [3,17,18]. In addition to cytokines, growth factors, and proteins, the MSCs secretomes contain exosomes carrying non-coding RNAs (miR-21, miR-24, and miR-26), further adding to the therapeutic potential of MSCs [17]. The AdMSC-derived secretomes have already exhibited proangiogenic, immunomodulatory, and neurotrophic activities that can be used for managing inflammatory, autoimmune, and neurodegenerative diseases [17,19]. In addition, AdMSC-derived exosomes accelerate wound healing by promoting angiogenesis, fibroblast, or keratinocyte proliferation, regulating inflammatory response, and remodeling of extracellular matrix [20]. The present study provides an overview of global AdMSC research. Understanding the leading journals, institutions, and funding agencies will help prospective researchers design future studies. The emerging trends will further help to decide the direction of their research.
Contrary to Web of Science (WoS), Scopus is available as a single database. In addition, the Scopus database is more accessible to individuals and provides free access to author and source information [12]. Furthermore, the Scopus database offers about 20% more coverage than WoS [21]. This is the primary reason for selecting the Scopus database in our study. The number of studies on AdMSC has increased over the past several years. This indicates the increased awareness among the research community regarding the potential clinical applications of AdMSC.
In a previous bibliometric analysis on AdMSC research that analyzed Table 4 The characteristics of top ten journals publishing on adipose-derived mesenchymal stem cell research.   [10]. As a result, the United States was identified as the most productive country in all three time periods [10]. However, our study identified China to be the most productive country. This disparity can be attributed to the fact that several journals indexed in Scopus are not available in the PubMed database (National Centre for Biotechnology Information) [21]. Our study identified Seoul National University (South Korea) as the most productive institute/university in AdMSC, with 72 articles published. A similar outcome was reported in another study that evaluated umbilical cord-derived mesenchymal stem cell research from the WoS database in which Seoul National University contributed 48 papers during the 1975 to 2017 period [22]. Similarly, the National Natural Science Foundation of China emerged as the top funding agency in umbilical cord-derived mesenchymal stem cell research [22]. This pattern was also identified in our study, indicating a similar research interest in AdMSC and umbilical cord-derived mesenchymal stem cell research. Furthermore, the National Natural Science Foundation of China (https://www.nsfc.gov.cn/english/site_1/index.html) has always shown an interest in funding research projects in the fields of medicine and plastic surgery [23].
The present study analyses the research trends in the Scopus database and peripherally gives a snapshot of AdMSC research progress. Although it provides data on the research productivity, a few limitations have to be considered. This study was purely based on the Scopus database and did not consider databases such as WoS, PubMed, Google Scholar, etc. Furthermore, false-positive and false-negative results might have slightly affected the result of the bibliometric study. We also did not exclude self-citations during analysis, which may impact the overall number of citations and h-index.

Conclusions
China was found to be the most productive country, whereas Seoul National University (South Korea) identified as the most productive institute/university in AdMSC research. In addition, the National Natural Science Foundation of China funded the most research studies in AdMSC research. China has a robust national and international collaboration in AdMSC research with the highest single country and multiple country publications. However, the top ten listed countries involved in AdMSC research have a low Multiple Country Publications ratio (MCP Ratio less than 0.50), indicating lower international collaboration. Although Stem Cell Research and Therapy journal published the highest number of articles on AdMSC research, maximum citations were received by Stem Cells and Development journal. The findings from this study indicate a progressive increase in interest among the research community towards AdMSC, suggesting promising prospects in the coming years. Furthermore, our study provides a fresh perspective of global AdMSC research, enabling us to understand the past, present, and future.

Funding
No substantial funding is to be stated.

Availability of data and material
The data that support the findings of this study are available in the form of supplementary material attached to the publication.

Ethics approval
Ethics committee approval is not required as there is no human or animal research.

Consent to participate
Not applicable.

Consent for publication
Not applicable.