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Download Ph.D. Student : Abbas Jafari Kermani Enrolment : 1 March 2009
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Ph.D. Student Enrolment Project Title : Abbas Jafari Kermani : 1 March 2009 : Identification of kinases that determine differentiation of human mesenchymal stem cells into osteoblastic cells and their use as therapeutic targets for modifying osteoblast differentiation and enhancing bone formation Supervisors : Professor Moustapha Kassem, Professor Matthias Dobbelstein Institute : Institute of Clinical Research Research Unit : Endocrinology Abstract: Osteoporosis is a systemic age-related disease that is characterized by reduced bone mass due to increased bone resorption by osteoclastic cells (recruited from hematopoietic cells) and decreased bone formation by osteoblastic cells (recruited from mesenchymal stem cells), resulting in bone fragility and increased fracture risk. Osteoporotic fractures are a major health problem in the elderly population, leading to significant morbidity, mortality, and enormous burden on health care services. The current therapy for osteoporosis is based on using drugs that inhibit osteoclastic bone resorption that lead to stabilization of bone mass but does not affect bone formation, although bone formation is usually decreased. Only one anabolic medication (i.e. increasing osteoblastic bone formation) is available for osteoporotic patients, which is parathyroid hormone injection, and thus there is a need for development of novel anabolic therapies. We recently screened a kinase inhibitor library to identify novel small molecules with potential to enhance osteoblastic differentiation of human mesenchymal stem cells (hMSC) and we identified one kinase inhibitor (KIx) that was found to enhance osteoblastic differentiation of hMSC and also other pre-osteoblastic cell lines. Also, by using heterotopic bone formation assay in immunedeficient mice, we showed that KIx enhances in vivo bone formation. The mechanisms by which KIx enhances in vivo bone formation and in vitro osteoblastic differentiation of hMSC is under investigation. Furthermore, we are studying the possible use of this kinase inhibitor as an anabolic drug for enhancing bone formation in bone-loss diseases. Also we will investigate the potential use of this kinase inhibitor for improving the therapeutic capacity of hMSC, for bone regeneration in cell-based therapy. These studies are pre-requisite for developing KIx into a candidate drug for further development to be used in therapy of bone-loss diseases. Keywords: Stem cell research
