Kim Yong Sang, Kim Yong Il, Koh Yong Gon
Center for Stem Cell & Arthritis Research, Department of Orthopaedic Surgery, Yonsei Sarang Hospital, Seoul, Republic of Korea.
Department of Stem Cell Research, TJC Life Research and Development Center, TJC Life, Seoul, Republic of Korea.
Knee. 2021 Jan;28:159-168. doi: 10.1016/j.knee.2020.11.021. Epub 2020 Dec 29.
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 × 10 cells; G4, 4.8 × 10 cells; G5, 9.6 × 10 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.
最近，使用间充质干细胞（MSCs）的基于细胞的组织工程方法已被用于治疗骨关节炎（OA）。然而，人滑膜来源的间充质干细胞（hSD-MSCs）的疗效尚未在犬OA模型中得到测试。本研究的目的是探讨关节内注射hSD-MSCs对犬OA模型的治疗效果。
60只比格犬接受手术操作以诱导OA，并在术后4周接受关节内注射。根据注射材料将犬分为五组（n = 12）：G1，假手术组；G2，注射磷酸盐缓冲盐水的对照组；G3、G4和G5，注射不同剂量hSD-MSCs的实验组（G3，2.4×10个细胞；G4，4.8×10个细胞；G5，9.6×10个细胞）。在注射后6周和24周进行磁共振成像（MRI）、组织病理学和免疫组织化学检查。
MRI显示，注射hSD-MSCs的组（G3-G5）在注射后24周滑膜炎有显著改善。组织病理学分析表明，这些组（G3-G5）在注射后6周软骨结构和蛋白聚糖染色也有显著改善，并在24周后进一步改善。免疫组织化学分析显示，注射hSD的组（G3-G5）之间I型和II型胶原蛋白水平有显著差异，表明其细胞外基质（ECM）组成与未受损的关节软骨相似。
我们的研究首次证明，关节内注射hSD-MSCs可通过恢复软骨、促进ECM合成和抑制炎症反应来改善犬OA的进展。
