Yong Sang Kim1, Yong Il Kim2, Yong Gon Koh3. 1. Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea. 2. Department of Stem Cell Research, TJC Life Research and Development Center, TJC Life, Seoul, Republic of Korea. 3. Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea. Electronic address: yonggonkoh@gmail.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.