In situ tissue regeneration - chemokine triggered cellular and molecular response of human mesenchymal stem cells

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Several chemokines have the potential to chemoattract bone marrow mesenchymal stem cells (MSC). Based on in situ heart and brain tissue repair studies, and on own results, we hypothesize that a cell therapy approach using chemokines will allow the in situ recruitment of MSC to sites of damaged or arthritic diseased cartilage, and their subsequent use for the directed regeneration of it. This approach comprises supportive bio-scaffolds and bioactive molecules promoting recruitment and chondrogenesis of MSC. Our research objective is to characterize chemokine triggered cellular and molecular responses of human bone marrow MSC. This includes proteomics of the chemokine secretion profile of cartilage and chondrocytes derived from normal donors (ND) and patients with osteoarthritis (OA), study of the chemotactic effect of selected chemokines on MSC, and chemokine receptor blocking with receptor specific antibodies and siRNA. Gene expression profiling will be performed to analyze the signalling network triggered by chemokines. To study the influence of a controlled chemoattractant release on MSC, a release system will be generated and applied in nude mice. This investigation will contribute to the establishment of a chemokine based in situ regeneration of tissues such as injured or OA diseased cartilage.