Jahagirdar, Balkrishna N., M.D.

HEMATOLOGY/ONCOLOGY

My lab studies the therapeutic utility of bone marrow derived Multipotent Adult Progenitor Cells (MAPC) in mouse models of various diseases. At present we are focusing on the Fanconi anemia knockout mouse model. Our group has discovered multi-potent stem cells in the adult human, mouse and rat marrow, called Multipotent Adult Progenitor Cells (MAPC). A high number of human MAPC can be culture expanded within a few months from just 15-20 ml of adult bone marrow. In a petri dish MAPC can make cells of the brain (neurons), liver (hepatocytes), heart (cardiomyocytes & endothelial cells) and most other organs. When injected intravenously into adult mice, MAPC integrate into and make blood, epithelium of the gut, lung and liver and the inner lining of blood vessels (endothelium). Because MAPC can be derived from a small quantity of patient’s own bone marrow and produce blood, replace the defective linings of the gut and the lungs, MAPC transplantation has the potential of correcting several diseases of the lung, gut and blood. The first step towards clinical MAPC transplantation would be to test it in animal models of human diseases. A disease that has both hematologic and epithelial abnormalities would be the ideal model to initially test the broad therapeutic usefulness of MAPC transplantation. Fanconi anemia (FA) is a multi-system disorder characterized by defective DNA repair mechanisms that predispose to hematologic and epithelial cancers, exquisite sensitivity to chemotherapy and radiation, aplastic anemia and myelodysplastic syndrome. FA-C knockout (FACKO) mice, exhibits several characteristics of human FA. Our studies are designed to transplant normal MAPC into FACKO mice and expose them to low doses of chemotherapy & radiation to select for the normal MAPC-derived cells and damage the FA cells. The hypothesis is that the transplanted normal MAPC will protect the FACKO mice from the effects of low dose chemotherapy & radiation and thus would correct the FA phenotype. We have established a breeding colony of the FACKO mice and are in a position to undertake the transplantation studies. If successful in this model, autologous MAPC transplantation may be used to treat many common adult diseases of the hematopoietic and epithelial systems.