Abstract / Summary
Abstract Mesenchymal stem cell-based therapies are a promising strategy for the regeneration of articular cartilage and management of knee osteoarthritis (KOA). Nevertheless, the comparative therapeutic efficacy of single versus repeated intra-articular injections of human adipose-derived mesenchymal stem cells (haMSCs) for cartilage preservation in animal models of osteoarthritis, particularly in the lateral and medial femoral condyles and intercondylar fossa, remain unclear. This study compared a single‑dose regimen with a two‑dose regimen for knee articular cartilage preservation in a rabbit model of surgically induced KOA. haMSCs were isolated, expanded in culture, and characterized in vitro by flow cytometry and trilineage differentiation assays. KOA was surgically induced via anterior cruciate ligament transection followed by medial and lateral meniscectomy (ACLTM). After surgery, the left knee joints of rabbits received intra-articular injection as follows: the negative control and vehicle control groups respectively received sterile saline and vehicle at weeks 6 and 9; the single-dose group received haMSCs at weeks 6 followed by vehicle at weeks 9; and two-dose group received haMSCs at weeks 6 and 9. Rabbits were sacrificed 18 weeks after surgery, and samples (whole knee joints and femoral condyles) were collected, processed, and analyzed. Changes in knee articular cartilage were assessed by macroscopic examination, histology, and immunohistochemistry. ACLTM induced the degeneration of the femoral condyles and intercondylar fossa, confirming the successful establishment of KOA in rabbits. No abnormal clinical signs were observed following haMSC treatment during the study period. Compared with saline, vehicle, and single-injection treatments, two intra-articular injections of haMSCs produced better macroscopic improvements of femoral condyles, resulting in smoother articular surfaces and improved ICRS scores, along with significantly reduced Mankin scores, particularly in the medial femoral condyle and intercondylar fossa. Immunohistochemistry showed that two haMSC injections enhanced type II collagen expression in articular cartilage, as evidenced by higher H-scores and a larger type II collagen-positive area. In contrast, a single injection achieved only limited improvement. Compared with the single-dose regimen, two intra-articular injections of haMSCs provided superior cartilage matrix preservation in the medial femoral condyle and intercondylar fossa in a rabbit model of KOA, while no improvement was observed in the lateral femoral condyle. These findings suggest that the dosing regimen may influence the cartilage-protective effects of haMSCs.