ORIGINAL RESEARCH ARTICLE Open Access b1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage Lesions

Mesenchymal stem cells (MSC) may have great potential for cell-based therapies of osteoarthritis. However, after injection in the joint, only few cells adhere to defective articular cartilage and contribute to cartilage regenera-tion. Little is known about the molecular mechanisms of MSC attachment to defective articular cartilage. Here, we developed an ex vivo attachment system, using rat osteochondral explants with artificially created full-thickness cartilage defects in combination with genetically labeled MSC isolated from bone marrow of human pla-cental alkaline phosphatase transgenic rats. Binding of MSC to full-thickness cartilage lesions was improved by serum, but not hyaluronic acid, and was dependent on the presence of divalent cations. Additional in vitro tests showed that rat MSC attach, in a divalent cation-dependent manner, to collagen I, collagen II, and fibronectin, but not to collagen XXII or cartilage oligomeric matrix protein (COMP). RGD peptides partially blocked the ad-hesion of MSC to fibronectin in vitro and to cartilage lesions ex vivo. Furthermore, the attachment of MSC to col-lagen I and II in vitro and to cartilage lesions ex vivo was almost completely abolished in the presence of a b1 integrin blocking antibody. In conclusion, our data suggest that attachment of MSC to ex vivo full-thickness car-tilage lesions is almost entirely b1 integrin-mediated, whereby both RGD- and collagen-binding integrins are in-volved. These findings suggest a key role of integrins during MSC attachment to defective cartilage and may pave the way for improved MSC-based therapies in the future. Key words: biochemistry; cellular biology; extracellular matrix; stem cell