Intra-articular injection of human synovium-derived mesenchymal stem cells in beagles with surgery-induced osteoarthritis.

Abstract

Recently, cell-based tissue engineering approaches using mesenchymal stem cells (MSCs) have been used to treat osteoarthritis (OA). However, the efficacy of human synovium-derived MSCs (hSD-MSCs) has not yet been tested in a canine model of OA. The purpose of this study was to investigate the therapeutic effects of intra-articular hSD-MSC injections in a canine OA model. Sixty beagles underwent surgical manipulation to induce OA and received intra-articular injection 4 weeks after surgery. The dogs were divided into five groups (n = 12) according to the injection material: G1, sham group; G2, control group injected with phosphate-buffered saline; G3, G4, and G5, experimental groups injected with different hSD-MSC dosages (G3, 2.4 × 10⁶ cells; G4, 4.8 × 10⁶ cells; G5, 9.6 × 10⁶ cells). Magnetic resonance imaging (MRI) and histopathological and immunohistochemical examinations were performed 6 and 24 weeks after injection. MRI revealed significant improvements in synovitis 24 weeks after injection in the hSD-MSC-injected groups (G3-G5). Histopathologic analyses showed that cartilage structure and proteoglycan staining were also significantly improved in these groups (G3-G5) 6 weeks after injection and improved further after 24 weeks. Immunohistochemical analysis revealed significant differences in the levels of collagen types I and II between the hSD-injected groups (G3-G5), indicating a similar extracellular matrix (ECM) composition to naïve articular cartilage. Our study demonstrated for the first time that intra-articular hSD-MSC injection ameliorates the progression of canine OA by restoring cartilage, promoting ECM synthesis, and inhibiting the inflammatory response.