The purpose of the study was to evaluate the effects of mesenchymal stem cell-extracellular vesicles (MSC-EVs) on chondrocyte proliferation in vitro and on cartilage repair in vivo following bone marrow stimulation (BMS) of focal chondral defects of the knee.
Six adult Göttingen minipigs received two chondral defects in each knee. The pigs were randomized to treatment with either BMS combined with MSC-EVs or BMS combined with phosphate-buffered saline (PBS). Intra-articular injections with MSC-EVs or PBS were performed immediately after closure of the surgical incisions, and at 2 and 4 weeks post-operatively. Repair was evaluated after 6 months with gross examination, histology, histomorphometry, immunohistochemistry, and micro-computed tomography (µCT) of the trabecular bone beneath the defect.
More bone was seen in the cartilage defect area in defects treated with MSC-EVs compared with PBS-treated defects (7.9% vs. 1.5%, p = 0.02). Hyaline cartilage represented less than one percent of the repair tissue in both groups. Using ICRS II histological scoring, defects treated with MSC-EVs scored lower on “matrix staining” (20.8 vs. 50.0, p = 0.03), “cell morphology” (35.4 vs. 53.8, p = 0.04), and “overall assessment” (30.8 vs. 52.9, p = 0.03). In addition, defects treated with MSC-EVs had lower collagen II and higher collagen I areal deposition. The subchondral bone had significantly higher tissue mineral densities in defects treated with MSC-EVs compared with PBS-treated defects (860 mg HA/cm3 vs. 838 mg HA/cm3, p = 0.02).
Intra-articular injections of MSC-EVs in conjunction with BMS led to osseous ingrowth that impaired optimal cartilage repair, while enhancing subchondral bone healing.