Mesenchymal stem cells and knee osteoarthritis: A bibliometric analysis

Abstract

Objectives:

Mesenchymal stem cells (MSCs) are characterized by self-renewal and multidirectional differentiation, indicating that they have great application prospects in the treatment of knee osteoarthritis (KOA). The purpose of this study was to explore the research status, hot spots and future research trends of the use of MSCs in KOA treatment and to provide a basis for research directions and applications in this field.

Methods:

We searched the Web of Science Core Collection database from 2012 to 2022 to identify literature related to the use of MSCs for the treatment of KOA. All the included studies were subjected to bibliometric analysis via Hiplot Pro and CiteSpace software to produce statistics and visual analyses of data, including the nation, institution, author, keyword and reference.

Results:

A total of 1537 studies were analyzed. These studies had been cited 41,916 times. The 3 countries with the greatest number of published papers were the USA (415), China (374), and Italy (130). Two U.S.-based institutions, i.e., Hospital for Special Surgery and Rush University, had the greatest number of published papers. The representative journals in this field were Stem Cells, Annals of Rheumatic Diseases, Osteoarthritis and Cartage and the American Journal of Sports Medicine. Keyword co-occurrence and co-citation reference analyses revealed that the key research theme in this field in the past decade has been the efficacy and mechanism of MSCs for treating KOA (articular cartilage). These findings preliminarily confirmed the clinical value of MSCs for treating KOA.

Conclusions:

The use of MSCs to treat KOA has great potential for clinical application and has been widely studied by researchers. The clinical efficacy and mechanism of action of MSCs are still the core content. In KOA treatment, adipose-derived MSCs, MSC-derived exosomes and the risk of MSC application are future research areas.

1. Introduction

Epidemiological studies have shown that osteoarthritis (OA) is a highly prevalent and disabling disease that affects more than 7% of the world’s population (approximately 528 million), of which knee osteoarthritis (KOA) accounts for approximately 85% of cases.^[1,2] Among elderly individuals (over 60 years of age), the prevalence of KOA is approximately 10% for males and 13% for females.^[3] KOA affects mainly middle-aged, elderly and obese people, and its clinical symptoms are pain, swelling, stiffness and decreased mobility.^[4,5] The main pathological characteristics of KOA are hypertrophy, apoptosis, cartilage matrix degradation and the ability to repair the imbalance of articular chondrocytes.^[6] At present, the main treatment methods for KOA are nonsteroidal anti-inflammatory drugs, opioid analgesics, intra-articular injection, and symptomatic slow-acting drugs for osteoarthritis (SYSADOAs); furthermore, surgery may be needed in some patients with poor drug treatment effects and poor prognoses.^[7–9]

Mesenchymal stem cells (MSCs) are pluripotent stem cells with the characteristics of self-renewal and multiple differentiation; they can migrate to the damaged site and secrete chemokines, cytokines and growth factors that aid in tissue regeneration. Moreover, they play anti-inflammatory, anti-withering and immune regulatory roles.^[10,11] Intra-articular injection of MSCs has been used to treat KOA, and preliminary results have suggested that MSCs can relieve knee pain and improve cartilage quality.^[12,13] However, several critical issues related to MSC therapy, including transplantation rejection, tumor formation risk, and ethical concerns, still need to be resolved before their widespread clinical application.

CiteSpace is a bibliometric software developed on the basis of structural hole theory and Thomas Kuhn scientific revolution theory.^[14] CiteSpace is used to conduct detailed data mining and analysis of literature in an academic field on the basis of the principle of metrological analysis and to show research hotspots, frontiers and evolutionary trends hidden in scientific literature in the form of a map.^[14] At present, there are no bibliometric studies on the use of MSCs to treat KOA. For this study, the knowledge base, research hotspots and trends of the use of MSCs in the treatment of KOA over the past 10 years were examined via bibliometric analysis. Relevant studies were collected from the Web of Science database, and directions for in-depth research and clinical application in this field were provided.

2. Materials and methods

2.1. Data collection

The data source of this study is the Web of Science Core Collection database (WOSCC). The inclusion criteria were as follows: the publication date ranged from January 1, 2012 to October 31, 2022; the document type is an article or a review only; the language was limited to English; the topic is the research and application of MSCs in KOA. The search strategy was as follows: TS = ([MSCs OR MSCs OR MSCs] AND [knee osteoarthritis OR KOA]). Through a literature search based on the above conditions, we obtained 1716 relevant studies published from 2012 to 2022. After the duplicate and ineligible studies (i.e., those that did not meet the inclusion criteria) were removed, 1537 articles were finally obtained, including 1113 articles and 424 reviews. The process and details of the literature retrieval process are shown in Figure 1.

Figure 1.

Flow chart of the literature screening and analysis methods.

2.2. Data statistics and visualization

CiteSpace (Version 6.1. R4) software and Hiplot Pro (https://hiplot.com.cn/) were used for data statistics and visual analysis. To evaluate the research hotspots, trends and frontiers of MSCs and KOA, we used CiteSpace to conduct cooperation network, co-occurrence and burst analyses. According to the given research purpose, the node types can be set as country, author, institution, keywords, journal or reference. The basic parameters of CiteSpace software are set as follows: the time slice is from 2012 to 2022, and each slice unit is 1 year. In the CiteSpace software, the Top N value is set to 50, and the overall map is simplified by using pathfinder, pruning the merged network, and minimum spanning tree clipping methods.

Additionally, we used CiteSpace software to calculate the burst indices of keywords and cocited references. The burst index reflects the sudden increase in node frequency in the spectrum – and the higher the index is, the stronger the sudden increase in node frequency in a certain period.^[14] Centrality refers to the importance of authors, countries, institutions, literature and keywords as media and is used to measure the importance of nodes in a map.^[15] Nodes with a centrality value exceeding 0.1 are called key nodes.^[15] The node size in the atlas indicates its occurrence frequency, the thickness of the connection between nodes indicates the connection strength, and the degree of node ring thickness is in direct proportion to the occurrence frequency reported in the literature.^[14,15]

3. Results

3.1. Publication outputs and citation trends by year

During the period from January 1, 2012 to October 31, 2022, the WOSCC included 1537 articles on topics related to MSCs and KOA, of which only 46 were published in 2012 and only 244 in 2021. The total number of citations of 1537 articles reached 41,916, with an average citation value of 27.27. The total number of citations reached 9506 in 2021. Through the analysis of published outputs and citations (Fig. 2A), we found that MSCs have received considerable attention and strong interest from researchers in the field of KOA treatment in the past 10 years.

Figure 2.

(A) Global trend of annual publications and citations related to MSC and KOA research from 2012 to 2022. (B) World map displaying the global distribution of publication contributions. (C) The 10 countries/regions with the most publications. KOA = knee osteoarthritis, MSCs = mesenchymal stem cells.

3.2. Publication contributions of countries/regions

From 2012 to 2022, a total of 1537 articles in the field of the use of MSCs as a treatment for KOA were published in 74 countries or regions worldwide (Fig. 2B). The top 10 countries with the greatest number of papers in this field were the USA, China, Italy, South Korea, England, Germany, Japan, the Netherlands, Spain and Australia (Fig. 2C), of which the USA and China are the main paper-producing countries. The above information indicates that the publishing contributions of various countries in this field vary greatly.

3.3. Bibliometric analysis of coauthors and institutions

We drew the author information of 1537 documents into the author cooperation network map (Fig. 3A). The results suggest that the map density (0.0079) of the authors’ cooperative network was low, which indicates that the cooperative relationships between authors were not close. The author’s cooperation network suggests that the main researchers in the field of MSCs for KOA are Sekiya Ichiro, Koga Hideyuki, Muneta Takeshi, Tsuji Kunikazu, Mafulli Nicola and Filardo Giuseppe. The authors with more than 20 articles in this field were Sekiya Ichiro and Koga Hideyuki. Their main research topics focused on the efficacy and mechanism of MSCs in articular cartilage. The top 10 authors according to the number of documents are shown in Figure 3B. A total of 356 institutions have published papers in this field. The density of the institutional cooperation network was 0.0093 (Fig. 4A), which indicates that the degree of cooperation among institutions was low. The top 10 documents are shown in Figure 4B. The hospital for special surgery had the highest number of documents, while Rush University and Tokyo Medical and Dental University both had 26 documents.

Figure 3.

(A) Network visualization of authors involved in studies on MSCs and KOA. (B) The top 10 productive authors. KOA = knee osteoarthritis, MSCs = mesenchymal stem cells.

Figure 4.

(A) CiteSpace visualization of institutions involved in the research of MSCs and KOA. (B) The top 10 productive institutions. KOA = knee osteoarthritis, MSCs = mesenchymal stem cells.

3.4. Analysis of top journals

The top 10 journals cited in the field of MSCs as a treatment for KOA were cited 7771 times in total, accounting for 18.54% of the total citations and demonstrating the academic contributions of these 10 journals in this field (Table 1). The most frequently cited journals were Osteoarthritis and Cartage, followed by Arthritis Research and Therapy and the American Journal of Sports Medicine. The average numbers of citations of papers included by Stem Cells and Annals of Rheumatic Diseases were 119.17 and 108.5, respectively. The research topics of these journals focused on joints, regenerative medicine, sports medicine, basic research and clinical applications, and their published articles represent the research focus and direction in this field in recent years.

Table 1.

The ranking of the top 10 journals with highest citations.

Rank	Journal	Citations	TP	2021 IF	2021 JCI	JCR
1	Osteoarthr Cartil	1264	50	7.507	1.83	Q1
2	Arthritis Res Ther	814	21	5.606	1.28	Q1
3	Am J Sports Med	803	58	7.010	2.17	Q1
4	J Orthop Res	783	31	3.103	1.17	Q2
5	J Bone Joint Surg Am Vol	719	9	6.558	2.21	Q1
6	Stem Cells	715	6	5.845	1.09	Q1
7	Plos One	711	25	3.752	0.88	Q2
8	Arthrosc-J Arthrosc Relat Surg	694	20	5.973	1.84	Q1
9	Ann Rheum Dis	651	6	28.003	4.31	Q1
10	Knee Surg Sports Traumatol Arthrosc	617	27	4.114	1.59	Q1

IF = impact factor, JCI = journal citation indicator, JCR = journal citation reports, TP = total number of publications.

3.5. Bibliometric analysis of co-occurring keywords and clusters

Keyword co-occurrence is a centralized expression of current research issues or concepts that can accurately describe current research hotspots.^[14] The visualization map of keyword co-occurrence is shown in Figure 5A. There were 11 high-frequency words counting more than 200 and 24 high-frequency words counting more than 100 (Table 2). In addition to the main keywords of this study, i.e., MSCs and KOA, the other high-frequency keywords in this field were articular cartilage, bone marrow, repair, intra-articular injection, therapy, stromal cell, platelet-rich plasma (PRP), differentiation, regeneration and autologous chondrocyte implantation.

Figure 5.

CiteSpace visualization of keywords involved in the research of MSCs and KOA. (B) Cluster analysis of keywords. KOA = knee osteoarthritis, MSCs = mesenchymal stem cells.

Table 2.

The top 30 keywords in co-occurrence frequency of MSCs and KOA.

Rank	Keyword	Count	Centrality	Rank	Keyword	Count	Centrality
1	Mesenchymal stem cell	849	0	16	Differentiation	166	0.03
2	Knee osteoarthritis	409	0.02	17	Cartilage	161	0.01
3	Articular cartilage	362	0	18	Regeneration	139	0.03
4	Osteoarthritis	304	0.01	19	Autologous chondrocyte implantation	130	0.01
5	Knee	276	0.01	20	In vitro	129	0.02
6	Bone marrow	240	0.02	21	Chondrogenic differentiation	121	0.03
7	Repair	227	0.01	22	Chondrocyte	115	0.03
8	Intra-articular injection	221	0.02	23	Cartilage repair	106	0.02
9	Stem cell	221	0.02	24	Adipose tissue	103	0.02
10	Therapy	207	0.01	25	Transplantation	99	0.02
11	Stromal cell	204	0.02	26	Defect	98	0.02
12	Platelet-rich plasma	190	0.04	27	Double-blind	94	0.03
13	Tissue	177	0.02	28	Growth factor	91	0.03
14	Expression	171	0.03	29	Subchondral bone	89	0.04
15	Hyaluronic acid	166	0.04	30	Synovial fluid	87	0.03

KOA = knee osteoarthritis, MSCs = mesenchymal stem cells.

We used the log likelihood ratio algorithm to cluster the keyword co-occurrence map (Fig. 5B), where the module value Q was 0.3718 > 0.3 and the average profile value S was 0.6928 > 0.5, which shows that the clustering results are highly reliable and reasonable. Nine tags were formed in this clustering, among which the first 6 categories were tissue engineering, gene expression, PRP, umbilical cord blood, subchondral bone and intra-articular injection. The keywords contained in each cluster are shown in Supplementary material S1, Supplemental Digital Content, https://links.lww.com/MD/P343.

3.6. Keyword bursts

Keyword burst analysis can show the transfer of research focus in different periods, which can help anticipate potential development trends and frontier research. The higher the strength is, the greater the influence. The keyword burst results in the field of MSCs for KOA are shown in Figure 6. In the past decade, the 2 keywords with the greatest burst intensity were transplantation (strength: 8.81) and exosome (strength: 10.03). From 2012 to 2017, the focus of research was on the repair of knee chondrocytes, whereas the focus was on transfer to PRP and cells from 2018 to 2019. The keywords of interest from 2020 to 2022 include exosome, replacement, cytokine and risk, which indicates that future research should focus on exosomes derived from MSCs, the impact of MSCs on the level of cytokines in the KOA microenvironment and the risk of MSC application.

Figure 6.

Top 20 keywords with the strongest citation bursts (sorted by the beginning year of the burst).

3.7. Analysis of cocited references and bursts

The knowledge base is formed in the cocited literature, and the research frontier is composed of the collection of cited documents that cite these knowledge bases.^[16] The results of the cocited reference analysis are shown in Figure 7. Table 3 shows the details of the top 10 cocited references. High-frequency studies have focused mainly on the clinical use of MSCs from different sources for treating KOA, the efficacy of MSCs in treating knee joint cartilage defects, and the role of MSCs combined with hyaluronic acid (HA) in treating KOA, indicating that the current research focus is whether MSCs are effective at treating KOA.

Figure 7.

CiteSpace visualization of cocited references.

Table 3.

Top 10 highly co-citation of cited references.

Rank	Count	Title	Year	Journal	First author
1	272	Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial	2014	Stem Cells	Jo CH
2	195	Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial	2015	Transplantation	Vega A
3	138	Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase I dose-escalation trial	2016	Stem Cells Transl Med	Pers YM
4	133	Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study	2013	Transplantation	Orozco L
5	124	Mesenchymal stem cell injections improve symptoms of knee osteoarthritis	2013	Arthroscopy	Koh YG
6	119	Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis	2012	Knee	Koh YG
7	108	Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study	2014	J Bone Joint Surg Am Vol	Vangsness CT
8	97	Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model	2017	Theranostics	Tao SC
9	96	Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up	2013	Arthroscopy	Wong KL
10	92	Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II)	2016	J Transl Med	Lamo-Espinosa JM

The burst analysis of the cocited references suggests that the research focused from 2012 to 2019 focused mainly on the effects or repairs of MSCs on articular chondrocytes, cartilage defects and the meniscus. Since 2020, research has focused on the clinical efficacy or mechanistic exploration of ADMSC- and MSC-derived exosomes in KOA (articular cartilage) (Table 4). Figure 8 shows the top 20 burst cocited references.

Table 4.

The main content of the 20 references with strong citations bursts.

No	Title (main content)	Strength
1	Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study	18.7
2	Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement	16.3
3	Intra-articular injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization to distant organs in rat massive meniscal defect	16.29
4	Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells	16.18
5	Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients	14.57
6	Mesenchymal stem cells as trophic mediators	13.87
7	Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source	12.16
8	Injectable mesenchymal stem cell therapy for large cartilage defects – a porcine model	11.7
9	Mesenchymal stem cells in arthritic diseases	11.4
10	Synovial fluid mesenchymal stem cells in health and early osteoarthritis: detection and functional evaluation at the single-cell level	11.4
11	Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study	10.93
12	Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone marrow stromal cells	10.24
13	Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part II	12.89
14	The clinical use of human culture–expanded autologous bone marrow mesenchymal stem cells transplanted on platelet-rich fibrin glue in the treatment of articular cartilage defects: a pilot study and preliminary results	10.91
15	Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis	10.41
16	Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis	11.18
17	Osteoarthritis	16.02
18	Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial	12.65
19	miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis	10.97
20	Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis	10.67

Figure 8.

Top 20 references with strong citation bursts (the red bar indicates high citations in that year).

4. Discussion

This study provides a bibliometric analysis of MSCs and KOA based on literature from the WOSCC database, which aims to summarize the research status and development trends in this field. This bibliometric analysis delineates the evolving landscape of MSC research in KOA therapeutics over the past decade. Leveraging 1537 publications from the WOSCC, we employed CiteSpace and Hiplot Pro to quantify global research outputs, map collaboration networks, and identify thematic shifts. Key findings reveal a surge in scholarly engagement, with the United States and China driving 51% of publications, whereas institutions such as Hospital for Special Surgery and researchers such as Sekiya Ichiro anchored pivotal contributions. Cluster analyses and keyword bursts further pinpointed 3 paradigm transitions: from early cartilage repair mechanisms to emerging frontiers in adipose-derived MSC applications, exosome-mediated therapies, and risk assessment frameworks. These data-driven insights not only validate the use of MSC-based strategies as a transformative avenue for KOA management but also establish a roadmap for prioritizing translational research and international cooperation in this rapidly advancing field.

From 2012 to 2022, 1537 studies involving MSCs and KOA were published worldwide. Our research results showed that both the output of papers and the number of citations demonstrated rapid growth, which indicates that the research and application of MSCs in KOA treatment has attracted the attention of researchers. Although many countries have published papers in this field, the USA and China have accounted for most publications, which shows a large difference in the research focus between countries. Additionally, the top 2 academic institutions (Hospital for Special Surgery and Rush University) with the greatest number of papers are in the USA. Sekiya Ichiro and Koga Hideyuki have published the most papers in this field, and they have exhibited very close cooperation. Their research has focused on the effects and mechanisms of MSCs on articular cartilage and the meniscus.^[17–19] The results from these authors may represent the basis and direction of research in this field. Although researchers have attached importance to MSCs for KOA, we found that the cooperation between countries, institutions and authors was still weak. Therefore, communication and cooperation among countries, authors and institutions should be strengthened to meet new challenges in this field. Additionally, the bibliometric results show that Osteoarthritis and Cartage, Arthritis Research and Therapy, American Journal of Sports Medicine, Stem Cells and Annals of Rheumatic Diseases are cited very frequently, which shows that the achievements in this field published by these journals have high academic value.

To better understand the research status of MSCs in treating KOA, we conducted keyword co-occurrence, keyword clustering and cocited reference analyses. The above analyses showed that the research in this field has focused on the repair effect of MSCs on articular cartilage and the efficacy of MSCs combined with PRR (or HA) intra-articular injection for treating KOA. Additionally, the bibliometric results revealed that the efficacy and mechanism of MSCs in the treatment of KOA were the main focus of research in the past decade. Burst words or cocited references are frequently used within a specific period, and the reflect the hotspots and directions in the trends of a field. The results of burst analysis of keywords and cocited references indicate that the frontiers or trends of future research are adipose-derived MSCs (ADMSCs), MSC-derived exosomes and the risk of MSCs treating KOA.

MSCs have advantages in the regeneration and repair of connective tissue, and their role is reflected mainly in their ability to self-differentiate to form tissue cells and promote the transformation of peripheral cells into defective tissue.^[20] In vitro experiments have shown that MSCs, as pluripotent stem cells, have the ability to differentiate into multiple cell types.^[21] Additionally, when MSCs are affected by the surrounding microenvironment, they can secrete cell activation factors to promote the regeneration of cells around them. This paracrine effect is called nutrition, and this effect is considered the main way to promote cartilage repair.^[22,23] In the past decade, many clinical studies on the use of MSCs in the treatment of KOA have been published, and many studies have argued that the use of MSCs has potential clinical efficacy.^[24–26] At present, the treatment method involves injecting MSCs into a cell suspension into the joint cavity, which is simple, easy to perform and less harmful to patients. Combination therapy with MSCs has also been a popular topic in recent research. For this type of therapy, MSCs are combined with PRP (or HA) and injected into the joint cavity. The use of MSCs combined with PRP (or HA) in the treatment of KOA has been studied by researchers, and many studies have shown that the use of MSCs combined with PRP (or HA) can reduce the pain of KOA patients and accelerate the clinical efficacy of cartilage repair.^[27–29] However, 1 study argued that joint cavity injection of MSCs combined with PRP had no advantage over injection of MSCs alone in improving knee joint function and pain,^[30] but the study lacked corresponding imaging or histological evidence. The clinical efficacy and mechanism of MSCs in the treatment of KOA have been the main topics of research in the past decade. Further research or advanced evidence-based justification is needed to address the limitations or blind spots in this field.

A study of the characteristics of MSCs from different tissues around the knee joint revealed that ADMSCs and bone marrow-derived MSCs (BM-MSCs) have strong proliferation and differentiation abilities, whereas stem cells from other regions have relatively weak proliferation and differentiation activities.^[31] ADMSCs and BM-MSCs are also often used as seed cells to treat KOA.^[31,32] ADMSCs are easy to obtain, can generate many homogeneous cells after amplification and have good chondrogenic differentiation ability, which may be the main reason that ADMSCs have been considered. The exocrine body secreted by MSCs is thought to play an important role in the repair of knee joint tissue.^[33] Therefore, exosomes from MSCs, which are easy to extract and have low immunogenicity and biological toxicity, have been used in research on KOA treatment.^[34–36] Specific nutrient factors carried by MSC-derived exosomes can regulate cell metabolism and the immune environment and play an anti-inflammatory role.^[36,37] These factors are conducive to restoring homeostasis of the extracellular matrix of chondrocytes, promoting cartilage regeneration, improving symptoms and delaying the progression of KOA. Although some progress has been made in identifying the mechanism by which MSC-derived exosomes treat KOA, there is still no strong evidence regarding the clinical efficacy of exosomes in experimental research, cytology, histology or imaging. Although some existing studies support the use of MSCs for treating KOA,^[12,23,28] issues such as transplantation rejection, tumor risk and ethics caused by MSCs still need to be studied further and resolved. Additionally, the separation, collection, transportation and storage of MSCs have high requirements for the age of donors, and in vitro amplification may reduce their proliferation and differentiation.^[38,39] These requirements or unknown risks have greatly hindered the application of MSCs in the treatment of KOA.

This study has several limitations. First, this study’s reliance on WOSCC and predefined keyword combinations may have omitted relevant studies from non-indexed sources, regional journals, or emerging terminology. Expanding searches to multidisciplinary databases, integrating semantic natural language processing tools for term variation detection, and establishing real-time literature tracking systems could mitigate retrieval biases and enhance comprehensiveness. Second, the data in this study are from the WOSCC only, so there is bias in data selection. Finally, the results of bibliometric analysis may differ from those of actual research. For example, we failed to capture some high-quality papers in the analysis process due to the low frequency of keyword occurrences or literature citations.

5. Conclusions

The number of papers published and cited on the topics of MSCs and KOA has increased annually, which means that the use of MSCs has great potential in the clinical treatment of KOA. Countries, institutions and authors need to strengthen cooperation to promote the development of MSCs for KOA treatment. In the past 10 years, research in this field has focused on the efficacy and mechanism of MSCs in treating KOA and has preliminarily confirmed the potential efficacy of MSCs in treating KOA. In the future, the research frontiers and trends in this field are likely ADMSCs, MSC-derived exosomes and the risk of MSC applications. The in-depth study of these topics should further clarify the role of MSCs in treating KOA.

Author contributions

Conceptualization: Linjin Lu, Zijun Ye.

Data curation: Linjin Lu.

Formal analysis: Linjin Lu.

Investigation: Linjin Lu, Haodong Liang, Kaimin Huang.

Methodology: Linjin Lu, Haodong Liang, Huan Li, Wei Huang.

Project administration: Zijun Ye.

Resources: Zijun Ye.

Software: Haodong Liang, Wei Huang.

Supervision: Zijun Ye.

Validation: Huan Li.

Visualization: Huan Li, Kaimin Huang, Wei Huang.

Writing – original draft: Linjin Lu, Haodong Liang, Huan Li, Kaimin Huang, Wei Huang, Zijun Ye.

Writing – review & editing: Linjin Lu, Haodong Liang, Huan Li, Kaimin Huang, Wei Huang, Zijun Ye.