INVESTIGATING THE VARIED THERAPEUTIC EFFECTS AND MECHANISMS OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS FROM DIFFERENT PASSAGES IN ATHLETES WITH OSTEOARTHRITIS

Abstract

Objective: To evaluate the therapeutic effectiveness of human umbilical cord mesenchymal stem cells (hUC-MSCs) from different passages (P3, P8, and P13) on knee osteoarthritis in athletes and to elucidate the cellular mechanisms underpinning these effects. Methods: This study characterized hUC-MSCs from P3, P8, and P13, assessing their stemness, migration, proliferation, and specific marker expression. Athlete-model rats with induced osteoarthritis were treated with hUC-MSCs from each passage. Therapeutic outcomes were measured by assessing knee swelling, discomfort levels, and through pathological examinations of the knee joints. Additionally, co-culture experiments evaluated the ability of hUC-MSCs to promote type II collagen synthesis and inhibit MMP13 expression in chondrocytes. Telomere length and telomerase activity were also measured to understand the variation in clinical efficacy across different passages. Results: P3 and P8 hUC-MSCs demonstrated enhanced osteogenic and chondrogenic differentiation potential compared to P13, which showed a predisposition toward adipogenic differentiation. The wound healing rate was significantly better in the P3 and P8 groups than in the P13 group. All groups displayed high levels of CD90 and CD105, confirming their mesenchymal characteristics, with reduced CD105 expression observed in the P13 group. In treating osteoarthritis, no significant differences in knee swelling, discomfort, Mankin scores, or pathological outcomes were noted between the P3 and P8 treatments; however, notable differences were observed between the P8 and P13 treatments. Co-culture experiments indicated that hUC-MSCs from P3 and P8 improved type II collagen synthesis and reduced MMP13 expression in chondrocytes more effectively than P13. Telomere analysis showed significantly shorter telomeres in P13, with telomerase activity being positive in P3 and P8 but absent in P13. Conclusion: The study concludes that hUC-MSCs from P3 and P8 passages hold superior therapeutic potential for managing knee osteoarthritis in athletes, likely due to their enhanced differentiation capabilities and telomerase activity compared to P13. These findings suggest that earlier passages of hUC-MSCs could be more beneficial for clinical applications in sports medicine focused on regenerative treatments for osteoarthritis.