In Situ Recruitment of Human Bone Marrow-Derived Mesenchymal Stem Cells Using Chemokines for Articular Cartilage Regeneration

Abstract

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.