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Skeletal/Bone

Molecular programming in osteoblast differentiation - Bone and cartilage can be formed from multipotent mesenchymal stem cells (MSCs). The prevelance of MSCs throughout the human body at all stages of life presents a readily accessible source of cells for regenerative therapies for these cell lineages. Recently Dr. M. Crisan has shown that perivascular cells, pericytes, are the precursors to MSCs. Despite the abundance of pericytes and the ease of ex vivo MSC culture, full exploitation of these cells is limited by the lack of robust lineage differentiation and our lack of knowledge of the molecular program directing differentiation.

Prof. H. van Leeuwen has developed an in vitro bone forming and mineralization model for human osteoblasts in which the molecular differentiation program has been profiled over time. Knowledge of the coordinated regulation of transcription factor networks is providing insights into the manipulation of patient cells for therapeutic purposes. Together with a spin-off company, Therosteon, Prof. H. van Leeuwen is using an integrated approach combining cellular and molecular approaches to develop of new therapeutics for osteoporosis and osteoarthritis.

MSCs and osteoblasts as the supportive microenvironment for hematopoietic stem cells MSCs with osteogenic potential are present in all hematopoietic tissues throughout development. There is strong evidence to suggest that HSCs reside in the bone marrow microenvironment at the endosteal surface in close association with osteoblasts and the bone matrix. To improve clinical treatments and the success rate of hematopoietic cell transplantation, a collaborative program (as described in the Blood section) combining the expertise of researchers such as Prof. H van Leeuwen on osteoblast differentiation/bone matrix formation and Prof. J. Cornelissen and Prof. E. Dzierzak on HSC isolation/growth/transplantation is underway.