Donor-tailored MSC-EVs for osteoarthritis phenotypes: source heterogeneity, engineering, and precision therapy
- 1State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Nanjing University, 321 Zhongshan Road, Nanjing, 210008 Jiangsu PR China
- 2Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Nanjing, PR China
- 3Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China
Abstract
Osteoarthritis (OA) is a highly heterogeneous degenerative joint disease comprising distinct clinical phenotypes. Recently, mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapeutic approach. While MSC-EVs from diverse sources share fundamental therapeutic mechanisms, they also possess source-specific properties. However, the therapeutic efficacy of EVs is limited in treatments without considering the OA phenotypic diversity. This review aims to elucidate the biological heterogeneity of MSC-EVs derived from diverse tissues (bone marrow, adipose, umbilical cord, and others). By comparing their molecular mechanisms in OA, we outline a potential donor-tailored approach that may inform matching of MSC-EV sources to predominant OA phenotypes. Furthermore, to overcome the limitations of native EVs in targeted delivery and in vivo half-life, we apply frontier bioengineering paradigms, including cellular preconditioning, genetic engineering, cargo loading, and integration with biomaterial scaffolds. Collectively, these advanced methodologies significantly enhance the targeting capability, intra-articular retention, and phenotype-specific therapeutic potency of MSC-EVs. Finally, we delineate current challenges and future research directions, establishing a theoretical foundation to accelerate the clinical translation of donor-tailored MSC-EVs as a precise and effective therapeutic approach for OA.
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BibTeX
@article{liu2026donortailored,
title = {{Donor-tailored MSC-EVs for osteoarthritis phenotypes: source heterogeneity, engineering, and precision therapy}},
author = {Zhao-jie Liu and Bin Liu and Yong Shi and Qing Jiang},
journal = {Journal of Nanobiotechnology},
year = {2026},
month = aug,
doi = {10.1186/s12951-026-04894-1},
url = {https://doi.org/10.1186/s12951-026-04894-1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Donor-tailored MSC-EVs for osteoarthritis phenotypes: source heterogeneity, engineering, and precision therapy
AU - Zhao-jie Liu
AU - Bin Liu
AU - Yong Shi
AU - Qing Jiang
PY - 2026
DA - 2026/08/07
JO - Journal of Nanobiotechnology
DO - 10.1186/s12951-026-04894-1
UR - https://doi.org/10.1186/s12951-026-04894-1
AB - Osteoarthritis (OA) is a highly heterogeneous degenerative joint disease comprising distinct clinical phenotypes. Recently, mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapeutic approach. While MSC-EVs from diverse sources share fundamental therapeutic mechanisms, they also possess source-specific properties. However, the therapeutic efficacy of EVs is limited in treatments without considering the OA phenotypic diversity. This review aims to elucidate the biological heterogeneity of MSC-EVs derived from diverse tissues (bone marrow, adipose, umbilical cord, and others). By comparing their molecular mechanisms in OA, we outline a potential donor-tailored approach that may inform matching of MSC-EV sources to predominant OA phenotypes. Furthermore, to overcome the limitations of native EVs in targeted delivery and in vivo half-life, we apply frontier bioengineering paradigms, including cellular preconditioning, genetic engineering, cargo loading, and integration with biomaterial scaffolds. Collectively, these advanced methodologies significantly enhance the targeting capability, intra-articular retention, and phenotype-specific therapeutic potency of MSC-EVs. Finally, we delineate current challenges and future research directions, establishing a theoretical foundation to accelerate the clinical translation of donor-tailored MSC-EVs as a precise and effective therapeutic approach for OA.
SN - 1477-3155
ER -