Comparative analysis of the therapeutic effects of mesenchymal stem cells and exosomes on cartilage regeneration: exploring their synergistic potential with hyaluronic acid for treating articular cartilage defects.

Purpose: Articular cartilage exhibits a low regenerative capacity and limited potential for self-renewal. Recent research has demonstrated that exosomes and mesenchymal stem cells (MSCs) significantly enhance cartilage repair by promoting cellular proliferation, increasing extracellular matrix synthesis, and modulating the immune response. Additionally, hyaluronic acid (HA), a critical component of synovial fluid, plays a key role in facilitating cell migration. This study aims to compare the regenerative effects of Wharton's jelly-derived MSCs, MSC-derived exosomes, and their combination with hyaluronic acid in the treatment of cartilage defects. Additionally, we seek to evaluate the impact of hyaluronic acid when combined with MSCs and exosomes through histological analysis in a rat model.

Methods: In this study, full-thickness cartilage defects were created in the trochlear grooves of both distal femurs in 48 adult rats. The knees were randomly assigned to six groups: Group I: Control-saline, Group II: Wharton's jelly mesenchymal stem cells (MSCs), Group III: Wharton's jelly MSC-derived exosomes (Exo), Group IV: Hyaluronic acid (HA), Group V: MSC and HA combination, and Group VI: Exo and HA combination. Each rat received a total of three intra-articular injections at weekly intervals, beginning two weeks post-surgery. Four weeks following the final injection, all rats were euthanized, and their femurs were dissected for analysis. All groups were assessed macroscopically using the International Cartilage Repair Society (ICRS) scoring system, following histological staining with hematoxylin-eosin (HE) and toluidine blue, and immunohistochemical staining with type II collagen antibodies. The quality of the repaired cartilage was subsequently evaluated according to the ICRS histological grading system by an independent, blinded observer.

Results: Macroscopic evaluations indicated that the ICRS scores of the MSC group (8.2 ± 0.7) were significantly higher (P < 0.05) than those of the control group (4.3 ± 0.7). The cartilage defects in the MSC group showed substantial repair, displaying the most effective cartilage regeneration among all groups. Furthermore, comparison between groups revealed that both the MSC and Exo groups demonstrated a higher rate of defect depth repair, a smaller demarcation border, and a smoother cartilage surface.

Conclusions: This study demonstrates that exosomes are as effective as stem cell therapies in promoting cartilage repair, suggesting that exosomes may serve as a viable alternative to cell-based therapies for cartilage damage. However, the addition of hyaluronic acid to stem cells and exosomes showed no significant enhancement in cartilage repair. Our findings highlight a potentially effective therapeutic strategy for the treatment of osteochondral cartilage defects.