1 Department of Orthopaedics, The Second Hospital of Shanxi Medical University , Taiyuan City, Shanxi Province, China .
2 Department of Orthopaedics, The Warren Alpert Medical School of Brown University/Rhode Island Hospital (RIH) , Providence, Rhode Island.
Tissue Eng Part A. 2017 Oct;23(19-20):1160-1168. doi: 10.1089/ten.TEA.2017.0046. Epub 2017 Sep 26.
Chemokine stromal cell-derived factor-1 (SDF-1) is a powerful chemoattractant for the localization of CXCR4-positive bone marrow mesenchymal stem cells (BMSCs) into the bone marrow. We studied the effects of SDF-1 on the cartilage defect repair by recruiting BMSCs and promoting its chondrogenic differentiation in vitro and in vivo. Chemotaxis analysis with Transwell plate showed that SDF-1 could recruit BMSCs through SDF-1/CXCR4 axis. Real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and Western blot results suggested that the levels of type II collagen and GAG were increased after incubating BMSCs with SDF-1 compared with the without SDF-1 group. More positive BrdU-labeled BMSCs were detected at the cartilage defect region in the SDF-1 + poly [lactide-co-glycolide] (PLGA) scaffold group (SP) in which those animals showed a smooth and transparent cartilage tissue with a strong staining of toluidine blue and type II collagen compared with the no-SDF-1 groups. ICRS score suggested that the repair effect in the SDF-1 + PLGA-treated animals was improved compared with PLGA scaffold group alone at 4 and 8 weeks after surgery; the repair effect from the SDF + PLGA-treated animals was significantly improved compared with the PLGA alone at 12 weeks after surgery. Our in vitro and in vivo results indicated the following: (1) SDF-1 could recruit the BMSCs into cartilage defect area. (2) SDF-1 induces BMSCs expressing type II collagen and GAG, which may accelerate the BMSCs transforming into chondrocytes under the cartilage microenvironment in vivo. (3) PLGA scaffold attached with SDF-1 remarkably promoted the cartilage defect repairing. The defected cartilage was filled with transparent cartilage 12 weeks after the surgery, which shared a similar structure with the adjacent normal cartilage. Taken together, this research provides a new strategy for cartilage defect repairing.
趋化因子基质细胞衍生因子-1(SDF-1)是一种强大的趋化因子,可将 CXCR4 阳性骨髓间充质干细胞(BMSCs)募集到骨髓中。我们研究了 SDF-1 通过募集 BMSCs 并促进其在体外和体内的软骨分化来修复软骨缺损的作用。Transwell 板的趋化分析表明,SDF-1 可以通过 SDF-1/CXCR4 轴募集 BMSCs。实时聚合酶链反应、酶联免疫吸附测定和 Western blot 结果表明,与无 SDF-1 组相比,BMSCs 孵育 SDF-1 后,Ⅱ型胶原和 GAG 的水平增加。在 SDF-1+聚乳酸-共-羟基乙酸(PLGA)支架组(SP)中,在软骨缺损区域检测到更多的 BrdU 标记的 BMSCs,与无 SDF-1 组相比,这些动物的软骨组织呈现出光滑透明的状态,甲苯胺蓝和Ⅱ型胶原的染色较强。ICRS 评分表明,与单独使用 PLGA 支架相比,在手术后 4 和 8 周时,SDF-1+PLGA 处理动物的修复效果得到改善;与单独使用 PLGA 相比,在手术后 12 周时,SDF-1+PLGA 处理动物的修复效果显著改善。我们的体外和体内结果表明:(1)SDF-1 可以将 BMSCs 募集到软骨缺损区域。(2)SDF-1 诱导 BMSCs 表达Ⅱ型胶原和 GAG,这可能会加速 BMSCs 在体内软骨微环境中转化为软骨细胞。(3)PLGA 支架与 SDF-1 结合可显著促进软骨缺损修复。手术后 12 周,缺损软骨被透明软骨填充,其结构与相邻正常软骨相似。综上所述,该研究为软骨缺损修复提供了一种新策略。