In Situ Recruitment of Human Bone Marrow-Derived Mesenchymal Stem Cells Using Chemokines for Articular Cartilage Regeneration
In Situ Recruitment of Human Bone Marrow-Derived Mesenchymal Stem Cells Using Chemokines for Articular Cartilage Regeneration
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DOI：
10.3727/096368914x681018
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发表时间：
2015-01-01
影响因子：
3.3
通讯作者：
Lee, Jin Woo
中科院分区：
文献类型：
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作者：
Park, Min Sung;Kim, Yun Hee;Lee, Jin Woo
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。关节软骨缺损由于损伤部位缺乏软骨细胞或BMSC而不能完全愈合。在这项研究中，趋化因子，这可能会导致一个完整的再生关节软骨的骨髓基质细胞趋化性进行了调查。CCR 2、CCR 4、CCR 6、CXCR 1和CXCR 2在正常BMSCs中表达，并且在用促炎细胞因子处理后显著增加。MIP-3 α和IL-8比MCP-1或SDF-1 α更能促进BMSC迁移。与MCP-1、SDF-1 α或PBS相比，IL-8和MIP-3 α显著增强BMSCs的趋化性。与含有PBS的支架相比，人BMSC向含有IL-8或MIP-3 α的移植支架的募集在体内显著增加。此外，含有IL-8和MIP-3 α的支架增强了比格犬膝关节软骨中骨软骨缺损部位的组织再生。因此，本研究表明IL-8和MIP-3 α是诱导受损关节软骨再生的候选者。
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-3 alpha and IL-8 more than by MCP-1 or SDF-1 alpha. IL-8 and MIP-3 alpha significantly enhanced the chemotaxis of BMSCs compared with MCP-1, SDF-1 alpha, or PBS. Human BMSC recruitment to transplanted scaffolds containing either IL-8 or MIP-3 alpha significantly increased in vivo compared to scaffolds containing PBS. Furthermore, IL-8- and MIP-3 alpha-containing scaffolds enhanced tissue regeneration of an osteochondral defect site in beagle knee articular cartilage. Therefore, this study suggests that IL-8 and MIP-3 alpha are the candidates that induce the regeneration of damaged articular cartilage.