Global Research Trends in Extracellular Vesicle–Based Therapy for Regenerative Medicine: A Bibliometric Analysis (2014–2024)

Ramya Lakshmi Rajendran; Atharva Anand Mahajan; Sathish Muthu; Sathish Kumar Rajappan Chandra; Prakash Gangadaran; Byeong-Cheol Ahn

doi:10.3390/bioengineering13020247

journal article Open Access Feb 20, 2026

Global Research Trends in Extracellular Vesicle–Based Therapy for Regenerative Medicine: A Bibliometric Analysis (2014–2024)

Ramya Lakshmi Rajendran

Atharva Anand Mahajan

Sathish Muthu

Sathish Kumar Rajappan Chandra Prakash Gangadaran

Byeong-Cheol Ahn

Bioengineering Vol. 13 No. 2 pp. 247 · MDPI AG

View at Publisher Save 10.3390/bioengineering13020247

Abstract

Background: Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents in regenerative medicine due to their ability to deliver bioactive molecules with enhanced stability and low immunogenicity. Their potential to replicate stem cell functions without the risks of live-cell transplantation has catalyzed a surge in global research. Objective: This study aims to perform a scientometric analysis of EV-based regenerative medicine research from 2014 to 2024, identifying publication trends, influential contributors, thematic clusters, and translational challenges. Methods: Data were retrieved from the Web of Science Core Collection and analyzed using CiteSpace software. The analysis included journal impact mapping, co-authorship networks, co-citation analysis, and thematic cluster identification. Metrics such as citation bursts, total link strength, and silhouette values were used to assess influence and thematic coherence. Results: The most prolific journals were Stem Cell Research & Therapy and International Journal of Molecular Sciences. China led in publication volume, while the USA dominated citation impact. Foundational works by Théry and Lai, including the MISEV guidelines, shaped methodological standards. Nine thematic clusters were identified, including oxidative stress, small EVs, mesenchymal stromal cells, muscle regeneration, and chronic kidney disease. A strategic shift toward engineered EVs and novel sources such as iPSCs and macrophages was evident. Key translational barriers include lack of standardization, scalability issues, and regulatory ambiguity. Conclusions: EV-based therapies are transitioning from foundational research to clinical application. Overcoming methodological and regulatory challenges will be critical to realizing their full therapeutic potential in regenerative medicine.

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References

44

[1]

Kumar "Extracellular vesicles as tools and targets in therapy for diseases" Signal Transduct. Target. Ther. (2024) 10.1038/s41392-024-01735-1

[2]

Archana "Theranostic extracellular vesicles: Emerging frontiers in neuromuscular disease diagnosis and therapy" Gene (2025) 10.1016/j.gene.2025.149640

[3]

Rajendran "Potential of mesenchymal stem cell-derived exosomes in the treatment of androgenetic alopecia" World J. Stem Cells (2025) 10.4252/wjsc.v17.i5.107078

[4]

Wang "Engineered extracellular vesicles derived from pluripotent stem cells: A cell-free approach to regenerative medicine" Burn. Trauma (2025) 10.1093/burnst/tkaf013

[5]

Chattopadhyay "Mesenchymal stem cell-derived exosomes: A paradigm shift in clinical therapeutics" Exp. Cell Res. (2025) 10.1016/j.yexcr.2025.114616

[6]

Ravi Mythili, V.M., Rajendran, R.L., Arun, R., Thasma Loganathbabu, V.K., Reyaz, D., Nagarajan, A.K., Ahn, B.-C., and Gangadaran, P. (2025). Emerging Strategies for Revascularization: Use of Cell-Derived Extracellular Vesicles and Artificial Nanovesicles in Critical Limb Ischemia. Bioengineering, 12. 10.3390/bioengineering12010092

[7]

Zhang "Engineered extracellular vesicles for tissue repair and regeneration" Burn. Trauma (2024) 10.1093/burnst/tkae062

[8]

Nargesi "Mesenchymal Stem Cell-derived Extracellular Vesicles for Renal Repair" Curr. Gene Ther. (2017) 10.2174/1566523217666170412110724

[9]

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

Wanrong Meng, Chuanshi He, Yaying Hao et al.

Drug Delivery 2020 10.1080/10717544.2020.1748758

[10]

Yang, J.J., He, S.Q., Huang, B., Wang, P.X., Xu, F., Lin, X., and Liu, J. (2025). A bibliometric and visualized analysis of extracellular vesicles in degenerative musculoskeletal diseases (from 2006 to 2024). Front. Pharmacol., 16. 10.3389/fphar.2025.1550208

[11]

Zhang "Global Research Trends in EV-Based Cell-Free Therapy for Osteoarthritis: A Bibliometric Analysis" Tissue Eng. Regen. Med. (2025) 10.1007/s13770-025-00749-2

[12]

Li, Z., Yan, J., Li, X., Chen, H., Lin, C., Zhang, Y., Gao, T., Zhang, Y., Shu, Y., and Pan, S. (2025). Advancements in extracellular vesicles biomanufacturing: A comprehensive overview of large-scale production and clinical research. Front. Bioeng. Biotechnol., 13. 10.3389/fbioe.2025.1487627

[13]

Lai "Proteolytic Potential of the MSC Exosome Proteome: Implications for an Exosome-Mediated Delivery of Therapeutic Proteasome" Int. J. Proteom. (2012) 10.1155/2012/971907

[14]

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Clotilde Théry, Kenneth W Witwer, Elena Aikawa et al.

Journal of Extracellular Vesicles 2018 10.1080/20013078.2018.1535750

[15]

Ibrahim "Exosomes as Critical Agents of Cardiac Regeneration Triggered by Cell Therapy" Stem Cell Rep. (2014) 10.1016/j.stemcr.2014.04.006

[16]

Zhang "Enhanced Therapeutic Effects of Mesenchymal Stem Cell-Derived Exosomes with an Injectable Hydrogel for Hindlimb Ischemia Treatment" ACS Appl. Mater. Interfaces (2018) 10.1021/acsami.8b08449

[17]

Chiaradia, E., Tancini, B., Emiliani, C., Delo, F., Pellegrino, R.M., Tognoloni, A., Urbanelli, L., and Buratta, S. (2021). Extracellular Vesicles under Oxidative Stress Conditions: Biological Properties and Physiological Roles. Cells, 10. 10.3390/cells10071763

[18]

Phinney "Concise Review: MSC-Derived Exosomes for Cell-Free Therapy" Stem Cells (2017) 10.1002/stem.2575

[19]

Murphy "Emerging role of extracellular vesicles in musculoskeletal diseases" Mol. Aspects Med. (2018) 10.1016/j.mam.2017.09.006

[20]

Kou "Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: A next generation therapeutic tool?" Cell Death Dis. (2022) 10.1038/s41419-022-05034-x

[21]

Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis

Laura Doyle, Michael Wang

Cells 10.3390/cells8070727

[22]

Chen, T., Chen, D., Su, W., Liang, J., Liu, X., and Cai, M. (2025). Extracellular vesicles as vital players in drug delivery: A focus on clinical disease treatment. Front. Bioeng. Biotechnol., 13. 10.3389/fbioe.2025.1600227

[23]

Zheng, Y., Wang, H., Li, X., Xie, J., Fan, J., and Ren, S. (2024). Extracellular vesicles in chronic kidney disease: Diagnostic and therapeutic roles. Front. Pharmacol., 15. 10.3389/fphar.2024.1371874

[24]

Wang "Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone-Related Diseases: Intercellular Communication Messengers and Therapeutic Engineering Protagonists" Int. J. Nanomed. (2024) 10.2147/ijn.s441467

[25]

Clinical Translation of Extracellular Vesicles

Aayushi Ghodasara, Aun Raza, Joy Wolfram et al.

Advanced Healthcare Materials 2023 10.1002/adhm.202301010

[26]

Zeng, Y., Qiu, Y., Jiang, W., Shen, J., Yao, X., He, X., Li, L., Fu, B., and Liu, X. (2022). Biological Features of Extracellular Vesicles and Challenges. Front. Cell Dev. Biol., 10. 10.3389/fcell.2022.816698

[27]

Cheng "Guidelines for clinical translation and commercialization of extracellular vesicles and exosomes based therapeutics" Extracell. Vesicle (2023) 10.1016/j.vesic.2023.100029

[28]

Huang "Emerging technologies towards extracellular vesicles large-scale production" Bioact. Mater. (2025)

[29]

Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina

Tom Driedonks, Linglei Jiang, Bess Carlson et al.

Journal of Extracellular Biology 2022 10.1002/jex2.59

[30]

Gupta "Biodistribution of therapeutic extracellular vesicles" Extracell. Vesicles Circ. Nucleic Acids (2023) 10.20517/evcna.2023.12

[31]

Exploring Regulatory Frameworks for Exosome Therapy: Insights and Perspectives

Jiaqing Shao, Jianhua Sun, Lan Hu et al.

Health Care Science 2025 10.1002/hcs2.70028

[32]

Challenges and Opportunities in Translating Extracellular Vesicles into Clinical Applications

Ciro Tetta, Giovanni Camussi

Stem Cells and Development 2025 10.1089/scd.2025.0051

[33]

Xue "Engineered Extracellular Vesicles in Chronic Kidney Diseases: A Comprehensive Review" Int. J. Nanomed. (2024) 10.2147/ijn.s452393

[34]

Engineered Extracellular Vesicles: A potential treatment for regeneration

Wen Cheng, Chenyu Xu, Yuran Su et al.

iScience 2023 10.1016/j.isci.2023.108282

[35]

Lu "CRISPR-Cas9 delivery strategies with engineered extracellular vesicles" Mol. Ther. Nucleic Acids (2023) 10.1016/j.omtn.2023.102040

[36]

Clinical applications of stem cell-derived exosomes

Fei Tan, Xuran Li, Jiaojiao Li et al.

Signal Transduction and Targeted Therapy 2024 10.1038/s41392-023-01704-0

[37]

Ye "Large extracellular vesicles secreted by human iPSC-derived MSCs ameliorate tendinopathy via regulating macrophage heterogeneity" Bioact. Mater. (2023)

[38]

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Joshua A. Welsh, Deborah C. I. Goberdhan, Lorraine O'Driscoll et al.

Journal of Extracellular Vesicles 2024 10.1002/jev2.12404

[39]

Yin "Cell-Based Therapies for Degenerative Musculoskeletal Diseases" Adv. Sci. (2023) 10.1002/advs.202207050

[40]

Jarrige, M., Frank, E., Herardot, E., Martineau, S., Darle, A., Benabides, M., Domingues, S., Chose, O., Habeler, W., and Lorant, J. (2021). The Future of Regenerative Medicine: Cell Therapy Using Pluripotent Stem Cells and Acellular Therapies Based on Extracellular Vesicles. Cells, 10. 10.3390/cells10020240

[41]

Hu "Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses" Acta Pharm. Sin. B (2021) 10.1016/j.apsb.2020.12.014

[42]

Shi "Macrophage-Derived Extracellular Vesicles: A Novel Therapeutic Alternative for Diabetic Wound" Int. J. Nanomed. (2025) 10.2147/ijn.s518655

[43]

Levy "Induced Pluripotent Stem Cell-Derived Extracellular Vesicles Promote Wound Repair in a Diabetic Mouse Model via an Anti-Inflammatory Immunomodulatory Mechanism" Adv. Healthc. Mater. (2023) 10.1002/adhm.202300879

[44]

Verma, N., and Arora, S. (2025). Navigating the Global Regulatory Landscape for Exosome-Based Therapeutics: Challenges, Strategies, and Future Directions. Pharmaceutics, 17. 10.20944/preprints202506.2532.v1

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Details

Published: Feb 20, 2026
Vol/Issue: 13(2)
Pages: 247
License: View

Authors

R

Ramya Lakshmi Rajendran

BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea

A

Atharva Anand Mahajan

Advanced Centre for Treatment, Research and Education in Cancer, Navi Mumbai 410210, Maharashtra, India

S

Sathish Muthu

Orthopaedic Research Group, Department of Orthopaedics, Coimbatore 641005, Tamil Nadu, India; Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Kanchipuram 631552, Tamil Nadu, India

S

Sathish Kumar Rajappan Chandra

Clinical Trial & Research Unit, Interdisciplinary Institute of Indian System of Medicine (IIISM), SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India

P

Prakash Gangadaran

Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea

B

Byeong-Cheol Ahn

BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea; Department of Nuclear Medicine, School of Medicine, Kyungpook National University Hospital, Daegu 41944, Republic of Korea

Funding

National Research Foundation of Korea Award: NRF-2022R1I1A1A01068652

Cite This Article

Ramya Lakshmi Rajendran, Atharva Anand Mahajan, Sathish Muthu, et al. (2026). Global Research Trends in Extracellular Vesicle–Based Therapy for Regenerative Medicine: A Bibliometric Analysis (2014–2024). Bioengineering, 13(2), 247. https://doi.org/10.3390/bioengineering13020247

Global Research Trends in Extracellular Vesicle–Based Therapy for Regenerative Medicine: A Bibliometric Analysis (2014–2024)

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