In Situ Recruitment of Human Bone Marrow-Derived Mesenchymal Stem Cells Using Chemokines for Articular Cartilage Regeneration.
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.
Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
Min Sung
MS
Park
Yun Hee
YH
Kim
Youngmee
Y
Jung
Soo Hyun
SH
Kim
Jong Chul
JC
Park
Dong Suk
DS
Yoon
Sung-Hwan
SH
Kim
Jin Woo
JW
Lee
D000293:Adolescent; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D018925:Chemokines / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects; D019707:Receptors, Chemokine / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*; D015203:Reproducibility of Results; D054457:Tissue Scaffolds / Q000737:chemistry; D055815:Young Adult
D018925:Chemokines; D018836:Inflammation Mediators; D019707:Receptors, Chemokine