Edwin M. Horwitz, MD, PhD
The long-range goal of our research is to develop novel cellular therapies for genetic disorders of children. Our efforts over the last several years have focused on using bone marrow mesenchymal cells to treat children with osteogenesis imperfecta, a metabolic bone disorder. Clinically, we conducted the first trial of bone marrow transplantation for children with a genetic disorder of osteoblasts, a terminally differentiated mesenchymal cell as well as the first trial of isolated, gene marked marrow mesenchymal cell therapy. Our studies provided the first clinical data demonstrating the therapeutic potential of mesenchymal cell transplantation in regenerative medicine. In the laboratory we have studied the biology of marrow cell differentiation to bone and showed that nonadherent cells most robustly, but not permanently, repopulate bone after BMT in mice. Further, we used retroviral integration site analysis to track the clonal progeny of a single stem/progenitor cell and unequivocally demonstrated that both bone and blood cells can be derived from a single marrow progenitor in our murine transplantation model. The results from our murine model closely reflect the outcome of our clinical trials allowing us to directly translate our scientific findings to the clinic in a meaningful time frame. We plan to build on our successful foundation of translational research in cell therapy by continuing to pursue more effective, rational treatment for children with osteogenesis imperfecta and also by broadening the scope of our work to other genetic disorders of childhood.