Park Min Sung, Kim Yun Hee, Jung Youngmee, Kim Soo Hyun, Park Jong Chul, Yoon Dong Suk, Kim Sung-Hwan, Lee Jin Woo
Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
Cell Transplant. 2015;24(6):1067-83. doi: 10.3727/096368914X681018. Epub 2014 Apr 22.
Bone marrow-derived mesenchymal stem cells (BMSCs) are a good cell source for regeneration of cartilage as they can migrate directly to the site of cartilage injury and differentiate into articular chondrocytes. Articular cartilage defects do not heal completely due to the lack of chondrocytes or BMSCs at the site of injury. In this study, the chemotaxis of BMSCs toward chemokines, which may give rise to a complete regeneration of the articular cartilage, was investigated. CCR2, CCR4, CCR6, CXCR1, and CXCR2 were expressed in normal BMSCs and were increased significantly upon treatment with proinflammatory cytokines. BMSC migration was increased by MIP-3α and IL-8 more than by MCP-1 or SDF-1α. IL-8 and MIP-3α significantly enhanced the chemotaxis of BMSCs compared with MCP-1, SDF-1α, or PBS. Human BMSC recruitment to transplanted scaffolds containing either IL-8 or MIP-3α significantly increased in vivo compared to scaffolds containing PBS. Furthermore, IL-8- and MIP-3α-containing scaffolds enhanced tissue regeneration of an osteochondral defect site in beagle knee articular cartilage. Therefore, this study suggests that IL-8 and MIP-3α are the candidates that induce the regeneration of damaged articular cartilage.
骨髓间充质干细胞（BMSCs）是软骨再生的良好细胞来源，因为它们可以直接迁移到软骨损伤部位并分化为关节软骨细胞。由于损伤部位缺乏软骨细胞或骨髓间充质干细胞，关节软骨缺损无法完全愈合。在本研究中，研究了骨髓间充质干细胞对趋化因子的趋化作用，这可能会导致关节软骨的完全再生。CCR2、CCR4、CCR6、CXCR1和CXCR2在正常骨髓间充质干细胞中表达，并在促炎细胞因子处理后显著增加。与MCP-1或SDF-1α相比，MIP-3α和IL-8对骨髓间充质干细胞迁移的促进作用更大。与MCP-1、SDF-1α或PBS相比，IL-8和MIP-3α显著增强了骨髓间充质干细胞的趋化作用。与含有PBS的支架相比，含有IL-8或MIP-3α的移植支架在体内显著增加了人骨髓间充质干细胞的募集。此外，含有IL-8和MIP-3α的支架增强了比格犬膝关节软骨骨软骨缺损部位的组织再生。因此，本研究表明IL-8和MIP-3α是诱导受损关节软骨再生的候选因子。
