Phat Thuan Nguyen
1,2 
, Phuc Van Pham
1,2 , Ngoc Bich Vu
3,2,1* 1 Stem Cell Institute, University of Science, Ho Chi Minh City, Vietnam
2 Vietnam National University, Ho Chi Minh City, Vietnam
3 Faculty of Biology-Biotechnology, University of Science, Ho Chi Minh City, Vietnam
Abstract
Introduction: Articular cartilage has a limited intrinsic capacity for regeneration following injury, particularly in cases of severe defects. Exosome-based therapy has emerged as a promising cell-free regenerative strategy, with increasing preclinical evidence supporting its therapeutic potential in cartilage repair. As previous studies have indicated that human adipose-derived mesenchymal stem cells (hADSCs) secrete regenerative factors, whereas human umbilical cord–derived mesenchymal stem cells (hUCMSCs) exert immunomodulatory effects, the combined use of exosomes from these two sources may have complementary therapeutic benefits.
Methods: In this study, exosome-enriched extracellular vesicles (EVs) isolated from hADSCs and hUCMSCs were combined, characterized, and evaluated in a cartilage defect model. The isolated EVs displayed a characteristic cup-shaped morphology under transmission electron microscopy, a size distribution ranging from 30 to 200 nm, and high expression levels of the exosomal markers CD9, CD63, and CD81.
Results: Treatment with the combined EVs formulation promoted the regeneration of medial femoral condyle defects at 12 weeks post-injury compared to untreated controls, as demonstrated by an improved macroscopic appearance and scoring, radiographic evaluation, and increased deposition of total collagen, glycosaminoglycans, and aggrecan.
Conclusion: The findings provide proof-of-concept evidence that a combined hADSC- and hUCMSC-derived EVs formulation represents a feasible cell-free approach to cartilage repair.