TYPE Review

PUBLISHED 10 October 2024

DOI 10.3389/fmed.2024.1462085

Global trends in the clinical

OPEN ACCESS utilization of exosomes in
EDITED BY
Saranya Wyles,
Mayo Clinic, United States
dermatology: a bibliometric
REVIEWED BY
Eiji Kawamoto,
analysis
Mie University, Japan
Min Wu,
Huazhong University of Science
Shiqin Tang1 , Pai Cai2 , Huina He1 , Yanan Tian1 , Ruiying Hao3 ,
and Technology, China Xin Liu4 , Tingting Jing3,5 , Yanyan Xu3,5* and Xiaojing Li1,3,5*
Beklem Bostancioglu,
1
Karolinska Institutet (KI), Sweden School of Clinical Medicine, Hebei University of Engineering, Handan, Hebei, China, 2 School
of Information Engineering, Suihua University, Suihua, Heilongjiang, China, 3 Affiliated Hospital of Hebei
*CORRESPONDENCE
University of Engineering, Handan, Hebei, China, 4 Handan Stomatological Hospital, Endodontics,
Xiaojing Li
Handan, Hebei, China, 5 Hebei Key Laboratory of Immunological Dermatology, Handan, Hebei, China
zlmdsh@126.com
Yanyan Xu
xuyanyan0308@163.com

RECEIVED 09 July 2024 The arena of exosomal research presents substantial emerging prospects
ACCEPTED 11 September 2024
PUBLISHED 10 October 2024 for clinical dermatology applications. This investigation conducts a thorough
CITATION analysis of the contemporary global research landscape regarding exosomes
Tang S, Cai P, He H, Tian Y, Hao R, Liu X, and their implications for dermatological applications over the preceding
Jing T, Xu Y and Li X (2024) Global trends
in the clinical utilization of exosomes decade. Employing bibliometric methodologies, this study meticulously dissects
in dermatology: a bibliometric analysis. the knowledge framework and identifies dynamic trends within this specialized
Front. Med. 11:1462085.
doi: 10.3389/fmed.2024.1462085
field. Contemporary scholarly literature spanning the last decade was sourced
from the Web of Science Core Collection (WoSCC) database. Subsequent to
COPYRIGHT
© 2024 Tang, Cai, He, Tian, Hao, Liu, Jing, Xu retrieval, both quantitative and visual analyses of the pertinent publications
and Li. This is an open-access article were performed utilizing the analytical software tools VOSviewer and Citespace.
distributed under the terms of the Creative
Commons Attribution License (CC BY). The A comprehensive retrieval yielded 545 scholarly articles dated from January 1,
use, distribution or reproduction in other 2014, to December 31, 2023. Leading the research forefront are institutions
forums is permitted, provided the original
author(s) and the copyright owner(s) are such as Shanghai Jiao Tong University, The Fourth Military Medical University,
credited and that the original publication in and Sun Yat-sen University. The most prolific contributors on a national
this journal is cited, in accordance with
accepted academic practice. No use,
scale are China, the United States, and South Korea. Among the authors,
distribution or reproduction is permitted Zhang Bin, Zhang Wei, and Zhang Yan emerge as the most published,
which does not comply with these terms.
with Zhang Bin also achieving the distinction of being the most cited.
The International Journal of Molecular Sciences leads in article publications,
whereas Stem Cell Research & Therapy holds the pinnacle in citation rankings.
Theranostics boasts the highest impact factor among the periodicals. Current
research hotspots in this area include Adipose mesenchymal stem cell-derived
exosomes(ADSC-Exos), diabetic skin wounds, cutaneous angiogenesis, and the
combination of biomaterials and exosomes. This manuscript constitutes the
inaugural comprehensive bibliometric analysis that delineates the prevailing
research trends and advancements in the clinical application of exosomes in
dermatology. These analyses illuminate the contemporary research focal points
and trajectories, providing invaluable insights that will inform further exploration
within this domain.

KEYWORDS

skin wounds, adipose-derived mesenchymal stem cells, exosome, bibliometrics, visual

analysis

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1 Introduction publication trends, author citation networks, and other aspects of

a topic (7).
The skin, which constitutes the body’s most extensive physical, The bibliometric analysis software VOS Viewer offers various
chemical, and immunological barrier, comprises the epidermis, visualization views, utilizing keywords, co-institutions, co-authors,
dermis, and subcutaneous tissue (1). Chronic exposure to the countries, and institutions. These views include Label Visualization,
external environment can precipitate skin instability and functional Density Visualization, Cluster Density Visualization, and Scatter
impairments, including pigmentary disorders, wounds, aging, and Visualization. By examining the size of circles in the visualization
immunological dysfunctions resulting in skin diseases. Exosomes, map, one can identify high-frequency keywords, prolific authors,
small extracellular vesicles (EVs), possess diameters ranging from as well as prominent countries and institutions. The creation of
40 to 150 nm. Their biogenesis entails three distinct stages: these views does not necessitate additional computer programs
the formation of intraluminal vesicles via plasma membrane and is characterized by ease of mapping, visually appealing views,
invagination, the inward budding of these vesicles to constitute and flexible data output (8). However, VOS Viewer has some
multivesicular bodies (MVBs), and subsequently, the facilitation of limitations, such as a fixed style of visualization mapping and
effective intercellular communication through the release of these limited clustering information extraction. During cluster analysis,
vesicle complexes, specifically exosomes (2–4). In recent years, it can only segment ranges by color without forming cluster labels
stem cell therapy has witnessed substantial advancement across through key information extraction.
diverse research domains, attributable to its multifunctionality, Another visualization software, Cite Space, focuses on
enhancement of regenerative factor secretion, and inherent self- assembling databases to analyze individual modules. Through
renewal properties. Exosomes are integral to the specialized similarity algorithms, it displays different temporal dimensions
functions of stem cells. As a cell-free therapeutic modality, of the atlas, which are used to visualize temporal changes,
exosomes facilitate the transfer of proteins, mRNA, and miRNA development trends, and fundamental changes in the research field
to regulate the functions of recipient cells, thereby circumventing (9, 10). Additionally, data can be processed flexibly, such as through
the associated rejection risks of cell-based therapies and offering de-weighting and slicing, which can enhance the accuracy and
substantial potential in clinical dermatological applications. efficiency of data analysis. However, there are some disadvantages,
According to a comprehensive review of the literature, the such as a relatively steep learning curve for beginners and software
application of exosomes in dermatological settings has captivated instability, which can hinder smooth data analysis.
the international scholarly community, yet it is noted that a In conclusion, while analyzing data using visualization
systematic bibliometric analysis in this area is currently absent. software, it is essential to also emphasize the reading of traditional
Consequently, this study employs the Web of Science Core reviews. Only by effectively combining both approaches can
Collection (WoSCC) as its primary data source, a database we accurately screen data and gain insights into emerging
esteemed as highly influential and ubiquitously acknowledged hotspots in the field.
within academic circles. A comprehensive analysis of all pertinent
literature in this domain is executed via the utilization of WoSCC.
Furthermore, distinguished software tools, namely CiteSpace and 2.2 Data sources
VOS Viewer, are implemented for advanced bibliometric and visual
analytics. This methodology seeks to elucidate the global research A structured query was initiated within the Web of Science
trajectory and emergent trends concerning the use of exosomes Core Collection (WoSCC) database based on the stipulated
in dermatological applications, delivering a nuanced interpretation criteria: ¬ The search theme was defined using the syntax:
of advancements in this sphere to discern principal contributors "TS = (("Exosomes") AND ("skin"))". ­: The search was confined to
and pivotal shifts, while concurrently shedding light on overarching content types “Article” and “Review Article”, with English specified
research trends. as the language. ®: The temporal scope extended from January 1,
2014, to December 31, 2023. ¯: The data retrieval culminated on
March 11, 2024, to mitigate possible biases introduced by daily
database updates. The corresponding link for this data retrieval
2 Research methodology and data is as follows:https://www.webofscience.com/wos/woscc/summary/
sources 3b781a47-f09f-4f09-95a2-816ef39da6c8-d38e046f/relevance/1. To
refine the dataset, exclusion criteria were meticulously applied
2.1 Research methodology to discard literature not pertinent to the research topic. Initially,
the search yielded 806 articles. Owing to potential duplicates or
Unlike general reviews, bibliometrics is a quantitative research data inconsistencies derived directly from the search query, a
methodology that relies on publication, citation, and text preprocessing step was implemented to enforce the aforestated
data to describe and analyze the dynamics and progress of exclusion criteria prior to analysis. Following rigorous examination
a discipline or field of study (5, 6). Bibliometric studies of each article, 545 valid publications were ascertained. The
yield results that encompass descriptive statistics as well as retrieved literature data was archived in TXT format, labeled as
information on keywords, texts, citations, authors, institutions, "full-text records and references". The exported literature records
and references. These studies examine the frequency, relevance, encompassed titles, authors, affiliations of research institutions
centrality, and clustering of authors and textual data, thereby often (research centers, universities, hospitals), abstracts, journals,
being employed by researchers to explore evolutionary patterns, publication dates, and references. Subsequently, this data was

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FIGURE 1
Illustrates the process of publication selection.

catalogued in an Excel database for detailed subsequent analysis across Europe (N = 10), Asia (N = 6), The Americas (N = 3), and
(Figure 1). Oceania (N = 1). Among these nations, China (N = 276, 45%)
and the United States (N = 84, 14%) surfaced as the principal
contributors in terms of publication volume, closely trailed by
South Korea (N = 47, 8%).
3 Bibliometric analysis of the papers It is notable that among the top 20 global institutions
catalogued in Table 1, Shanghai Jiao Tong University in China
3.1 Number of papers published boasts the most substantial representation (N = 19). Closely
following are esteemed institutions like The Fourth Military
Annual fluctuations in publication volumes can, to a significant Medical University (N = 17, 8%) and Sun Yat-sen University
degree, mirror changes in research themes, emerging trends, (N = 17, 8%) from other countries.
and prospective directions in development. Within the corpus of Subsequent to the initial analysis, visualizations were
545 articles analyzed in this study, contributions were made by constructed for countries contributing three or more publications
authors spanning 54 countries and 958 institutions, collectively (Figures 3A–C), wherein links between nodes depict the robustness
representing 21,752 researchers. These articles appeared in 220 of collaborative ties, and thicker lines denote a higher frequency
distinct journals and cited 28,354 references across 3,824 different of co-authored publications between two nations. Node hues
publications. Figure 2 delineates the temporal distribution of delineate distinct clusters. This graphical depiction illustrates
publications within the domain of exosome and skin-related China as the predominant cluster among the publishing nations in
research. Overall, the past decade has demonstrated a generally this area of research, unveiling a marked imbalance in publication
upward, albeit fluctuating, trend in this field, with 2014 recording distribution and a significant manifestation of the "head effect."
the nadir of publication volume and reaching an apex in the year By developing a visual network map of institutional
2022. collaborations (Figures 4A, B), our analysis uncovered a substantial
partnership between Shanghai Jiao Tong University and Wenzhou
Medical University, as well as Central South University—these
3.2 Institutions and countries institutions exhibiting the highest number of publications.
Furthermore, collaborations were consistently observed among
This investigation engaged in a comprehensive analysis of Zhejiang University, Sun Yat-sen University, Sichuan University,
publication volumes across 97 countries to ascertain which nations and Central South University. Institutions such as the University
have substantially contributed to research in exosomes and skin- of Virginia demonstrated significant connections with Old
related fields over the preceding decade. Table 1 delineates the Dominion University, University of Oxford, and The University of
foremost 20 countries and institutions, predominantly situated Queensland, each from distinct nations.

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FIGURE 2
Annual publication volume in exosomes and skin-related research over the past decade.

TABLE 1 Top 20 countries and institutions in exosomes and skin-related research field.

Rank Country Counts Percent Institution Counts Percent

1 China 276 45% Shanghai jiao tong univ 19 9%

2 USA 84 14% Fourth mil med univ 17 8%

3 South Korea 47 8% Sun yat sen univ 17 8%

4 Italy 33 5% Huazhong univ sci & technol 15 7%

5 Germany 18 3% Sichuan univ 15 7%

6 France 17 3% Tongji univ 11 5%

7 Spain 16 3% Jilin univ 10 5%

8 United Kingdom 16 3% Wenzhou med univ 10 5%

9 Japan 15 2% Jiangsu univ 9 4%

10 Iran 12 2% Southern med univ 9 4%

11 Poland 11 2% Cent soudi univ 8 4%

12 Australia 10 2% Fudan univ 8 4%

13 Brazil 9 1% Nanjing med univ 8 4%

14 Canada 8 1% Zhejiang univ 8 4%

15 Singapore 8 1% China med univ 7 3%

16 Switzerland 8 1% Korea univ 7 3%

17 Austria 7 1% Shandong univ 7 3%

18 India 7 1% Xi an jiao tong univ 7 3%

19 Sweden 7 1% Zunyi med univ 7 3%

20 Romania 6 1% Chinese peoples liberal army gen hasp 6 3%

3.3 Author analysis the leading trio of cited authors comprising Zhang B (N = 171),
Théry C (N = 127), and Zhang Y (N = 106) as documented
The citation frequency of a scholarly article serves as a critical in Table 2. Drawing upon this data, we devised a collaboration
metric for gauging its academic impact. Among authors globally network diagram of authors who have each published a minimum
recognized for their prolific output, a total of 3,662 contributors of two papers (Figures 5A, B), encompassing 356 authors who met
engaged in research pertaining to exosomes and skin, with the this criterion. Authors were distinctly clustered, with appearance
top ten authors each having authored five or more papers. Within frequencies denoted by color variations; each node in the diagram
this cohort, five authors were cited more than 100 times, with symbolizes an author, with node size mirroring the author’s

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FIGURE 3
Visualization of countries in exosomes and skin-related research field (A–C).

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FIGURE 4
Visualization of institutions in exosomes and skin-related research field (A,B).

publication volume. The lines interconnecting nodes signify the leading to the generation of a shared citation network diagram
collaborative relationships among authors. Notably, Zhang Bin, (Figures 5C, D). Among these, Zhang B emerged as the most
Zhang Wei, Hu Dahai, Li Yan, and Shen Kuo exhibited the eminent and extensively connected author, collaborating closely
largest nodes, indicative of their extensive collaboration and prolific with authors including Zhang Bin, Cho Byong Seung, and Park
publication output. Further scrutiny revealed that upon applying a Gyeong-Hun. These scholars actively partake in collaborations with
minimum citation threshold of 20, 137 authors satisfied the criteria, their less prolific counterparts, thereby fostering the advancement

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TABLE 2 Top 10 authors and collaboratively cited authors in exosome Figure 6B. The graph segregated into four primary color clusters,
and skin-related research over the past decade.
with a prominent abundance of red and green nodes denoting
Rank Authors Document Co- Citations significant interconnectivity among these clusters. Conversely, the
cited pale yellow nodes were fewer in number compared to the blue
authors nodes, suggesting an area for enhancement in the shared citation
1 Zhang, Bin 9 Zhang, B 171 count within the pale yellow cluster, potentially due to the content
and scholarly impact of the included publications.
2 Zhang, 7 Thery, C 127
Wei The dual-mapping overlay of journals delineates the
relationships between the citing and the cited journals, with
3 Zhang, Yan 7 Zhang, Y 106
the left side representing the citing journals and the right side
4 Qian, Hui 6 Li, X 105 the cited journals. As illustrated in Figure 7, the yellow pathways
5 Shi, Hui 6 Zhang, JY 105 denote significant citation relationships, illustrating that research
6 Hu, Dahai 6 Raposo, G 86 disseminated in Molecular Biology and Genetics journals is
predominantly cited by journals in the fields of Molecular Biology
7 Cho, 6 Lai, RC 76
Byong
and Immunology. The purple citation trajectories suggest that
Seung outputs from Molecular Biology and Genetics journals are
frequently referenced in disciplines such as Physics, Materials
8 Xu, 5 Hu, L 70
Wenrong Science, and Chemistry.

9 Li, Yan 5 Kalluri, R 68

10 Fang, Hui 5 Wang, L 68

3.5 Co-citation references and
bibliographic bursts
of research related to exosomes and skin, and facilitating scholarly
communication and exchange. From January 1, 2014, to December 31, 2023, a total of 28,354
co-citation references pertaining to research on exosomes and skin
were recorded. Within the foremost 10 co-citation references (see
3.4 Journal analysis Table 5), each reference was cited collectively no fewer than 50
times.
The articles were disseminated across a total of 220 journals. Employing VOSviewer, a co-citation network view (Figure 8A)
The top ten journals are enumerated in Table 3. International was constructed, selecting references that had garnered at least 20
Journal of Molecular Sciences (N = 43) spearheaded the selection citations. In Figure 8A, entities are represented in three distinct
with 855 citations and an average citation per article of 19.9, thereby colors; red denotes the most prolific references, succeeded by
securing the premier position. Following in close succession, green, and subsequently blue. Intriguingly, a heightened co-citation
Stem Cell Research and Therapy (N = 38) boasts the highest strength is observed between the red and blue categories. Larger
citation frequency, amassing a total of 1,933 citations. Frontiers in circles within the graph signify higher citation counts, thereby
Immunology (N = 16) claimed the third position. The publication reflecting the perceived scholarly impact of the references. Notable
with the most elevated impact factor was Theranostics (IF = 12.4). references including (11, 12, 13) demonstrate robust co-citation
In accordance with data presented in Table 4, it is noteworthy relationships.
that among the top ten most cited journals, six boast citations Subsequently, utilizing CiteSpace configured with a temporal
exceeding 500. Stem Cell Research & Therapy leads with the highest span from January 1, 2014, to December 31, 2023, and partitioning
citation tally (N = 981), succeeded by International Journal of each year into individual time slices, with "references" designated as
Molecular Sciences (N = 887), Scientific Reports (N = 702), PLOS the node type, resulted in the generation of 559 nodes as per these
One (N = 688), Journal of Investigative Dermatology (N = 603), stipulated parameters (Figure 8B).
Journal of Extracellular Vesicles (N = 539), Proceedings of the The concept of a citation burst refers to the intense frequency
National Academy of Sciences (PNAS) (N = 430), Stem Cells with which a reference is cited by scholars within a specific field
(N = 403), Theranostics (N = 386), and Frontiers in Immunology over a defined period. When a collection of articles is consistently
(N = 382). The publication boasting the highest impact factor is the cited, this phenomenon leads to the formation of concept clusters
Journal of Extracellular Vesicles (IF = 16). (14). In this analysis, CiteSpace identified 25 references exhibiting
Employing VOS Viewer, an initial total of 220 journals were significant citation bursts. As depicted in Figure 9, references
filtered based on a minimum publication criterion of two, from are organized according to their burst initiation year, with each
which 82 journals were selected for further analysis. A network respective bar symbolizing an individual year. The red lines denote
graph was generated of these journals (Figure 6A), showcasing a precipitous increase in citations for a particular reference during
International Journal of Molecular Sciences and Stem Cell Research a specific year.
& Therapy as nodes of high connectivity, indicative of their prolific The most pronounced citation burst, registering a strength of
publication output. Subsequently, further filtering was applied with 14.67, was recorded in the research conducted by Jieyuan Zhang’s
a threshold of a minimum shared citation count of 20, leading team (12), focusing on "Exosomes released from human induced
to the inclusion of 3,824 journals in the shared citation network pluripotent stem cells-derived MSCs facilitate cutaneous wound
graph. Of these, 392 journals were incorporated as illustrated in healing by promoting collagen synthesis and angiogenesis." Closely

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FIGURE 5
Visualization of Authors in exosome and skin-related research field (A,B); Visualization of collaboratively cited authors in exosome and skin-related
research field (C,D).

TABLE 3 Top 10 journals focusing on exosome and skin-related research in the past decade.

Rank Journal IF Publications JCR Citations Average

(2024) citation/publication
1 International Journal of Molecular 6:2 43 Q2 855 19.9
Sciences

2 Stem Cell Research & Therapy 7.5 38 Q2 1933 50.9

3 Frontiers in Immunology 7.3 16 Q2 361 22.6

4 Frontiers in Bioerigineering and 5.7 14 Q3 238 17.0

Biotechnology

5 International Journal of Nanomedicine 8.0 14 Q2 429 30.6

6 Journal of Nanobiotechnology 10.2 14 Q1 329 23.5

7 Cells 6.0 12 Q2 515 42.9

8 Frontiers in Cell and Developmental Biology 5.5 12 Q2 237 19.8

9 Scientific Reports 4.6 12 Q2 664 55.3

10 Theranostics 12.4 9 Q1 1028 114.2

following this is the study by Bin Zhang’s team on "Huc MSC- An incisive examination of the burst references presented
Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous in Figure 9 and Table 6 indicates that 18 of these articles
Wound Healing," which manifested a citation burst strength of pertain to investigations on the role of exosomes in skin healing,
specifically those originating from mesenchymal stem cells (MSCs).
12.94 (13). It is particularly notable that both studies were authored
Moreover, seven articles delve into elucidating the characteristics,
by Chinese scholars, each demonstrating burst strengths exceeding
mechanisms, and functional roles of exosomes. These analyses
10.0, with sustained citation prominence from 2016 to 2020. The substantiate that the citation burst strengths of these 25 references
third-ranked article, by burst strength (9.39), is titled "Extracellular span from 3.61 to 14.67, exhibiting a sustained impact lasting
vesicles: exosomes, microvesicles, and friends." between two and five years.

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TABLE 4 Top 10 most cited journals in exosome and skin-related research in the past decade.

Rank Co-cited journal H index IF (2024) JCR Co-citations

1 Stem Cell Research and Therapy 76 7.5 Q2 981

2 International Journal of Molecular Sciences 162 6.2 Q2 887

3 Scientific Reports 213 4.6 Q2 702

4 Plos One 332 3.7 Q3 688

5 Journal Of Investigative Dermatology 201 6.5 Q2 603

6 Journal Of Extracellular Vesicles 65 16 Q1 539

7 PNAS 771 11.1 Q1 430

8 Stem Cells 229 5.2 Q2 403

9 Theranostics 97 12.4 Q1 386

10 Frontiers in Immunology 124 7.3 Q2 382

3.6 Keywords and research hotspots a temporal keyword timeline that delineates the evolving research
hotspots and dynamic trends in the application of exosomes
Keywords encapsulate the quintessence of scholarly texts, within dermatological studies. This visualization provides a
serving as pivotal access points for literature searches. An analysis chronological perspective on the field’s progression, thereby
of keywords within a specific field can reveal both current illuminating emerging focal areas and guiding future research
focal points and prospective trends. Of the 2,598 keywords directions. The clustering graph is evaluated using the Modularity
subjected to analysis via VOS viewer, with a minimal occurrence Q and Weighted Mean Silhouette (S) indices to assess structural
threshold of five, 195 keywords surpassed this benchmark. Upon integrity and cohesion. This approach reveals a noteworthy
clustering and calculating the aggregate connection strength of division structure, indicated by a Q value greater than 0.3, and
these 195 keywords, a visualization manifesting keyword clusters a reasonable clustering coherence, as suggested by an S value
was generated (Figure 10A), where larger circles denote higher above 0.5 (16). The present analysis reveals that the keyword
keyword strength and denser lines between nodes indicate more clustering module, quantified by a Modularity Q value of 0.7365,
frequent co-occurrence of keywords. In the overlaid visualization significantly exceeds the threshold of 0.3, and the Weighted
map (Figure 10B), color-coded temporal segments illustrate the Mean Silhouette (S) value of 0.8721, which also surpasses the
evolution of keyword focal areas, with early-stage keywords critical value of 0.5, collectively suggesting a well-rationalized
depicted in navy blue and recent focal points in yellow-green. and distinctly defined clustering structure. In Figure 12, spanning
Detailed in Table 7, employing Citespace, the top 20 keywords were the years 2020 to 2023, the predominant keywords encapsulate
compiled, with the foremost three appearing over 100 times. Based themes including disease, adipose tissue, conditioned medium,
on frequency analysis, we identify the global research emphases, microvesicles, stromal cells, biomarkers, expression, exosome, cells,
underscored by interests in exosomes, extracellular vesicles, wound biogenesis, differentiation, collagen, angiogenesis, wound healing,
healing, and other relevant terms. migration, bone marrow, regeneration, alpha-2-macroglobulin,
Subsequent to employing CiteSpace for the cluster analysis injury, wound repair, fibroblast proliferation, skin rejuvenation,
of keywords, depicted in Figure 11, keywords were systematically growth factor, and rejuvenation. This comprehensive array
categorized into ten principal clusters, namely: #0 adipose tissue; highlights foundational and emergent areas of inquiry within the
#1 roles; #2 biology; #3 wound healing; #4 stem cells; #5 protein; field.
#6 vesicles; #7 diabetic wound; #8 extracellular vesicles; and #9
differentially expressed genes. Each cluster, denoted by identifiers
such as #0, #1, etc., represents a cohesive assembly, with larger
clusters encompassing a more substantial number of constituents
4 Discussion
(15).
By scrutinizing the timeline, one can discern the dynamic 4.1 General information
evolution of research focal points, as denoted by the keywords,
spanning from January 1, 2014, to December 31, 2023. This In the present investigation, we extracted bibliographic data
timeline encapsulates the emergence and attenuation of pivotal from the Web of Science Core Collection (WoSCC) and undertook
themes, capturing the ascension and recession of specific topics. a visualization analysis of this corpus utilizing tools such as
Keywords within identical clusters are aligned horizontally, CiteSpace and VOS Viewer. We explored the dimensions of
arrayed in chronological order from left to right, illustrating the the research findings, specifically examining annual publication
temporal progression from earlier to more recent developments. volume, contributing authors, affiliated institutions, pertinent
The prevalence of keywords within each cluster underscores keywords, involved countries, publishing journals, and referenced
the developmental magnitude and significance of that particular sources. As depicted in Figure 2, an analysis of the overarching
cluster in advancing research within the domain. Employing trend reveals a fluctuating yet ascendant trajectory in publication
CiteSpace for a comprehensive keyword analysis, we constructed volume over the preceding decade, with a nadir in 2014 and an

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FIGURE 6
Collaboration network visualization of journals in exosome and skin-related research in the past decade (A) and co-citation collaboration network
visualization of journals (B).

apex in 2022. Recent scholarly attention has coalesced around the in research contributions within this arena. Notably, the country
domain of exosomes and dermatological studies, with China, the analysis reveals a pronounced top-heavy distribution, with a select
USA, and South Korea distinguishing themselves as frontrunners few nations dominating the scholarly output, which suggests

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FIGURE 7
Dual mapping of journals in exosome applications in dermatology research over the past decade.

TABLE 5 Top 10 journals in exosome applications in dermatology per article, thereby securing the premier position in the field.
research cited over the past decade.
The most frequently cited journal is Stem Cell Research &
Rank Co-cited reference Citations Therapy(N = 981). Noteworthily, amongst both publishing and
heavily cited journals, Theranostics boasts the highest impact
1 Zhang B, 2015. stem cells, v33, p2158, doi: 80
factor (IF = 12.4).
10.1002/stem.l771 (13)
Author Zhang, Bin emerges as the preeminent scholar in terms
2 Zhang JY, 2015, j transl med, vl3, doi: 74
of both publication volume (N = 9) and citations (N = 171),
10.1186/s12967-015-0417-0 (12)
affirming his status as a pivotal contributor within this research
3 Valadi H, 2007, nat cell biol, v9, p654, doi: 67 domain. Zhang engages in extensive collaboration with notable
10.1038/ncb1596 (11)
peers including Zhang, Wei, Wang, Xujie, Hu, Dahai, Han,
4 Hu L, 2016, scirep-uk, v6. doi: 61 Shichao, Su, Linlin, among others. This research team, led by
10.1038/srep32993 (53)
Zhang, specializes in investigating the role of Mesenchymal
5 Théry C, 2018, j extracell vesicles, v7, doi: 60 Stem Cell-Derived Exosomes (MSC-Ex) in the arena of skin
10.1080/20013078.2018.1535750 (54) wound healing (17–20). Their investigations have elucidated that
6 Kalluri R, 2020, science, v367, p640, doi: 59 MSC-Ex significantly contributes to wound regeneration and
10.1126/science.aau6977 (55) cell proliferation via the activation of Wnt4, thus significantly
7 Raposo G, 2013, j cell biol, v200, p373, doi: 59 enhancing the process of skin wound healing (13).
10.1083/jcb.201211138 (56) Zhang Wei, holding the global second rank in publication
8 Shabbir A, 2015, stem cells dev, v24, p1635, 58 volume, has fervently pursued research focused on the healing of
doi: 10.1089/scd.2014.0316 (57) skin wounds and mitigation of scar formation through the study of
9 Fang S, 2016, stem cell transl med, v5, p1425, 56
exosomes derived from ADSC-Exos and human amniotic epithelial
doi: 10.5966/sctm.2015-0367 (58) cells-derived mesenchymal stem cells (21–23). Among the top ten
most cited references, the preponderance focuses on the role and
10 Théry clotilde, 2006, curr protoc cell biol, 52
vchapter 3. doi: mechanisms of mesenchymal stem cell-derived exosomes in skin
10.1002/0471143030.cb0322s30 (59) wound repair, complemented by several studies delving into the
general functions of exosomes. Consequently, the corroborated
data substantiates that the international academic community is
the presence of limited collaborative networks and a deficiency significantly engaged in investigating the role of mesenchymal
in proactive international cooperation. Enhanced international stem cell-derived exosomes in skin wound repair and the intricate
collaboration is imperative for the progression of this scientific mechanisms involved.
field, as cooperative endeavors are pivotal in nurturing its growth
and facilitating further development.
In the global institutional landscape, Shanghai Jiao Tong 4.2 Hotspots and frontiers
University emerges as the leader in publication volume,
highlighting its substantial and enduring engagement with The analysis of high-frequency keywords facilitates the
research in the realms of exosomes and dermatology. Journal discernment of pivotal research hotspots and evolutionary trends
ranking analysis illustrates that the International Journal of within specific scientific domains (24). Utilizing keyword co-
Molecular Sciences leads with the highest publication count occurrence analysis has delineated the primary trajectories and
(N = 43), amassing 855 citations and an average of 19.9 citations research hotspots pertinent to exosomes and skin, revealing

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FIGURE 8
Visualization of co-citation references in exosome and skin-related research over the past decade.

significant developments and thematic shifts. Employing keyword but additional terms also surfaced, including ‘wound healing,’
clustering and temporal analyses, not only were core keywords such ‘expression,’ ’mesenchymal stem cells,’ ‘angiogenesis,’ and others,
as ‘exosome,’ ‘extracellular vesicles,’ and ‘microvesicles’ highlighted, illustrating a rich tapestry of interconnected research areas. These

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FIGURE 9
Top 25 co-cited references in exosome and skin-related research over the past decade.

keywords encapsulate the dynamic hotspots and emerging frontiers materials such as umbilical cord, adipose tissue, and bone marrow
within the domain of exosome research and skin, underscoring the (25, 36).
critical aspects under investigation. Our analysis indicates that, over the past decade, exosomes
Exosomes, defined as extracellular vesicles ranging from 30 sourced from ADSC-Exos have emerged as the predominant
to 150 nm in diameter, serve as critical conduits for intercellular focus of research within the realm of skin-related applications.
communication within the skin’s cellular framework (25). Particularly, the application of ADSC-Exos in diabetic wound
In recent years, mesenchymal stem cells (MSCs) have repair has predominated, with a concentration on enhancing
captured the focused attention of the global scientific community. vascularization and protein synthesis. Numerous researchers
Characterized by their self-renewal capabilities and multipotent have dedicated their efforts to augmenting wound healing rates
by targeting specific differentially expressed genes through the
differentiation potential, these cells have been extensively explored
deployment of exosomes derived from mesenchymal stem cells.
across diverse scientific disciplines. Mesenchymal stem cells
Skin wound healing represents a multifaceted reparative
primarily originate from embryonic stem cells (ESCs) and induced
process, characterized by hemostasis, inflammation, proliferation,
pluripotent stem cells (iPSCs) (26–29), demonstrating a remarkable
and tissue remodeling, and involves intricate interactions among
ability to differentiate into various cell types including adipocytes,
diverse cytokines and components of the extracellular matrix
chondrocytes, and myocytes, contingent upon their tissue origin (ECM). Vascular formation serves as a critical determinant of
(30). outcomes in diabetic wound healing (37). Exosomes sourced
It is clear that mesenchymal stem cells, originating from a from ADSC-Exos have demonstrated potential in enhancing
variety of sources, produce exosomes that exhibit distinct functions wound healing in diabetic patients by accelerating vascular
and characteristics. Exosomes derived from mesenchymal stem formation, thereby amplifying the therapeutic potential for diabetic
cells have been demonstrated to play pivotal roles in skin wounds (38, 39). Wang et al. (40) have engineered a bioactive
wound repair and tissue regeneration (31, 32),notably facilitating hydrogel incorporating exosomes derived from ADSC-Exos, which
angiogenesis at injury sites (33), enhancing the speed of wound facilitates enhanced vascular formation and expedited wound
healing processes (34, 35), and are conveniently sourced from healing in diabetic patients. In their research, Wang et al. observed

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TABLE 6 Main content of the top 25 co-cited journals in exosome and skin-related research over the past decade.

Rank Strength Main research content

1 6.2–5 Extracellular vesicles derived from human umbilical cord mesenchymal stem cells mitigate hepatic fibrosis.

2 3.77 Composition, biological functions, diagnostic and therapeutic potential of extracellular vesicles.

3 14.67 Extracellular vesicles derived from human mesenchymal stem cells promote collagen synthesis and angiogenesis to facilitate
cutaneous wound healing.

4 12.94 Extracellular vesicles derived from mesenchymal stern cells convey Wnt4. thereby promoting wound healing.

5 9.39 A comprehensive review of the mechanisms, characteristics, and functions of extracellular vesicles.

6 7.44 Research on the promotion of wound healing by extracellular vesicles derived from mesenchymal stem cells.

7 4.09 The paracrine mechanisms of mesenchymal stem cell therapy.

8 7.23 Extracellular vesicles derived from human umbilical cord mesenchymal stem cells potentiate angiogenesis and facilitate
vascular regeneration via the Wnt4/β-catenin pathway.

9 6.51 The biological characteristics and physiological functions of extracellular vesicles.

10 3.95 Extracellular vesicles derived from human adipose-derived mesenchymal stem cells expedite skin wound healing by
optimizing the properties of fibroblasts.

11 8.5 The communication role of extracellular vesicles in diverse cell types.

12 6.6 The mechanisms, characteristics, and functions of extracellular vesicles.

13 6.25 Extracellular vesicle-derived microRNAs from umbilical cord mesenchymal stem cells inhibit the differentiation of
myofibroblasts by suppressing the transforming growth faclor-beta/SMAD2 pathway involved in the wound healing process.

14 6.04 Extracellular vesicles derived from human endothelial progenitor cells facilitate skin wound healing through Erk1/2
signaling pathway activation.

15 4.89 Extracellular vesicles derived from platelet-rich plasma enhance re-epithelialization of chronic skin wounds in a diabetic rat
model by activating YAP pathway.

16 4.62 Extracellular vesicles released by keratinocytes regulate melanocyte pigmentation deposition.

17 4.42 Exosomes secreted by mesenchymal stem cells facilitate endothelial cell angiogenesis through transfer of miR-125a.

18 4.39 Definition and function of extracellular vesicles.

19 4.23 Extracellular vesicles containing CD63, derived from bone marrow- mesenchymal stem cells, facilitate the extracellular
transport of Wnt3a and enhance proliferation, migration, and angiogenesis in dermal fibroblasts.

20 3.84 Exosomes derived from human fibroblasts expedite wound healing in a mouse model of hereditary diabetes mellitus.

21 3.61 Extracellular vesicles derived from human amniotic epithelial cells accelerate wound healing and suppress scar formation.

22 5.01 Extracellular vesicles derived from human umbilical cord mesenchymal stem cells mediate the alleviation of bum-induced
excessive inflammation through the modulation of miR-181c.

23 4.63 Exploration of the Characteristics, Functions, and Mechanisms of Extracellular Vesicles

24 3.82 Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles

25 6.08 Remodeling of Extracellular Matrix by Adipose-Derived Mesenchymal Stem Cell-Secreted Extracellular Vesicles: Promoting
Scarless Skin Repair.

that the deployment of circ-Astn1-modified exosomes from ADSC- Compared to other types of MSCs, ADSCs-Exos are more effective
Exos significantly bolsters endothelial cell proliferation and wound and can secrete many of the cytokines associated with wound repair
healing in diabetic wound management (41). Research conducted while maintaining the characteristics of MSCs (43–46). Studies
by the Guo group demonstrated that miR-125b-5p, isolated from indicate that in diabetic skin wounds, ADSCs-Exos accelerate
ADSC-Exos and identified via differential gene expression analysis, healing by promoting macrophage polarization towards the M2
likely plays a pivotal role in targeting ACER2 for reparative type, enhancing anti-inflammatory cell counts, and stimulating
functions in ischemic muscles associated with type 2 diabetes fibroblast proliferation and migration, as well as tissue angiogenesis
(42). (47–49). Currently, numerous challenges persist in applying
The use of exosomes in skin wounds mitigates the risks exosomes to cutaneous wound repair. The application of exosomes
associated with cell transplantation and demonstrates significant from various sources in wound treatment faces challenges due to
potential in cell-free regenerative medicine. Recently, MSCs have their short duration, as they are rapidly cleared from the application
been recognized for their crucial role in tissue regeneration site and have a short half-life in vivo, potentially limiting their
and wound repair, facilitating angiogenesis, modulating ECM long-lasting effects (50). This analysis suggests that future research
remodeling, skin barrier repair, and accelerating wound closure. will likely focus on extending the retention time of exosomes on

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FIGURE 10
Visualization of keyword network in exosome and skin-related research (A) and overlay visualization of keywords (B).

wound surfaces by integrating them with biomaterials, without applications, notable contributions emerge from China, the
compromising their biological activity, to develop treatments for United States, and South Korea. Herein lies a meticulous
skin diseases using ADSCs-Exos (51, 52). exploration of this phenomenon:
After conducting a comprehensive bibliometric analysis of In recent years, China has significantly increased its investment
the research field concerning EVs in relation to dermatological in biomedical research, particularly in cutting-edge areas such as

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FIGURE 11
Clustering of keywords in exosome and skin-related research.

FIGURE 12
Timeline graph of key words in exosome and skin-related research.

stem cell technology and EVs for wound healing. Government samples and data. For instance, national initiatives such as the
initiatives, including targeted financial aid, establishment of Major Science and Technology Projects aim to transcend key
advanced research platforms, and attraction of international technological barriers and promote the translation and application
talent, have catalyzed rapid advancements in related studies. of scientific achievements. Furthermore, the Science, Technology
Moreover, China’s vast patient population and extensive and Innovation 2030 Major Project includes regenerative medicine
clinical resources have provided an invaluable repository of and precision healthcare, crucially supporting research on

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TABLE 7 Top 20 keywords with highest frequency in exosome and instance, initiatives like the K-BIO (Korea Biotechnology Industry
skin-related research in the past decade.
Promotion Plan) bolster biotechnology and regenerative medicine
Rank Frequency Centrality Year Keywords sectors, facilitating expedited industrial growth. Comprehensive
support, encompassing research grants, business assistance, and
1 169 0.07 2014 Exosome
talent cultivation, underscores South Korea’s commitment to
2 153 0.01 2016 Extracellular
advancing EVs and skin research on a global scale. Participation in
vesicles
international research projects and hosting academic conferences
3 104 0.08 2015 Wound
further promotes transnational collaboration and enhances global
healing
contributions in EVs and skin research.
4 97 0.05 2014 Expression
In summary, the significant contributions of China, the
5 93 0.03 2016 Mesenchymal United States, and South Korea in extracellular vesicles and
stem cells dermatological studies stem from their robust scientific capabilities,
S 80 0.1 2014 Skin abundant research resources, and steadfast government support.
7 74 0.06 2015 Angiogenesis Through continuous technological breakthroughs, particularly in
8 54 0.01 2018 Stem cells
the processes of EV extraction, purification, characterization,
and functional studies, these countries have achieved pioneering
9 50 0.03 2016 Proliferation
results. Policy formulation and strategic planning have provided
10 48 0.11 2014 In vitro
a substantial guarantee for the rapid development of this field.
11 47 0.07 2015 Cells Looking ahead, as research deepens and technologies mature,
12 44 0.15 2015 Differentiation the prospects for EV applications in dermatological care, wound
13 43 0.01 2017 Therapy
healing, and anti-aging treatments are poised to expand further.

14 42 0.09 2015 Stromal cells

15 39 0.1 2017 Mechanisms

16 39 0.04 2017 Repair 4.3 Limitation

17 38 0.02 2015 Microvesicles
In this investigation, the WoSCC was selected as the data
18 36 0.05 2016 Migration
source, recognized widely for its exemplary quality as a digital
19 36 0.05 2018 Inflammation
literature resource and its suitability for rigorous bibliometric
20 30 0.05 2017 Regeneration analysis. However, it is pertinent to acknowledge certain limitations
inherent in this study. Given that databases often harbor duplicate
entries, subjective biases may influence the de-duplication process.
EVs and skin through policy backing and funding assurance.
The dataset was confined to English-language manuscripts
Furthermore, emphasis on research infrastructure, notably
through the establishment of national key laboratories and categorized exclusively as "Articles" or "Review Articles" from the
engineering research centers, has facilitated deepened exploration past decade, a constraint that may inadvertently exclude other
into EVs and skin studies. seminal works. Despite these constraints, the analysis delineated
As a global leader in research and innovation, the United States herein continues to illuminate cutting-edge trends in exosome
has consistently maintained high levels of investment in applications within dermatological research, offering substantial
biomedical research. With numerous world-class research insights to experts in the arena.
institutions and universities, coupled with a robust funding
framework, the United States provides significant backing for
EVs and skin research. Efforts to accelerate clinical translation of
research outcomes have enabled the swift application of relevant 5 Conclusion
technologies and products. For example, initiatives such as the
NIH funding programs encompass a broad spectrum, including Our study leveraged bibliometric analysis using VOSviewer
EVs and skin research, significantly advancing United States and CiteSpace to evaluate geopolitical entities, academic
innovations in this field. Additionally, stringent regulation institutions, authors, journals, and emerging research trends.
and policy frameworks governing clinical trials underscore the Fluctuations in annual publication rates highlight varying levels of
United States’ government commitment to ensuring the effective research emphasis among different nations. Notably, China, the
translation of novel therapies, including EVs. United States, and South Korea exhibit high publication volumes,
South Korea emerges as the third-highest contributor in with China demonstrating a distinctive leadership role. However,
this field, achieving notable milestones in biomedical research, other nations display potential for enhanced publication output.
particularly in dermatological aesthetics and anti-aging. The Furthermore, fostering closer international collaboration is crucial
Korean government places a significant emphasis on biotechnology for elucidating novel therapeutic mechanisms.
and regenerative medicine, supporting research institutions and Our analysis identifies current research hotspots, particularly
enterprises through policy formulation and strategic planning. extracellular vesicles derived from ADSC-Exos, with a focus on
Moreover, active collaboration with international research skin repair in diabetic wound healing. Prospective directions may
institutions fosters global progress in EVs and skin research. For involve integrating biomaterials with EVs to develop biocarriers

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Tang et al. 10.3389/fmed.2024.1462085

that maintain EV bioactivity while enhancing durability, which Funding

is crucial for advancing EV applications in skin wound repair.
Additionally, research trends in skincare and anti-aging are The author(s) declare that no financial support was received for
experiencing continued annual growth. the research, authorship, and/or publication of the article.
In conclusion, this study provides valuable insights for the
global scholarly community engaged in advanced research on EV
applications in dermatology.
Conflict of interest
Author contributions The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be
ST: Conceptualization, Data curation, Formal analysis, construed as a potential conflict of interest.
Investigation, Methodology, Project administration, Software,
Visualization, Writing−original draft. PC: Data curation,
Methodology, Visualization, Writing−original draft. HH: Formal
analysis, Project administration, Writing−original draft. YT: Publisher’s note
Formal analysis, Methodology, Writing−original draft. RH: Data
curation, Formal analysis, Writing−original draft. XL: Data All claims expressed in this article are solely those of the
curation, Methodology, Writing−original draft. TJ: Data curation, authors and do not necessarily represent those of their affiliated
Methodology, Writing−original draft. YX: Data curation, Funding organizations, or those of the publisher, the editors and the
acquisition, Resources, Writing−original draft. XL: Funding reviewers. Any product that may be evaluated in this article, or
acquisition, Project administration, Resources, Supervision, claim that may be made by its manufacturer, is not guaranteed or
Writing−original draft. endorsed by the publisher.

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