Activation, proliferation and differentiation of a distinct phenotype of stem cells, called pancreatic oval cells, are observed after pancreatic injuries. Under certain physiological conditions, oval cells can act as bipotential progenitors of the different types of epithelial cells of the pancreas, the ducts, acinar and islet cells. Because pancreatic oval cells and hepatic oval cells share an uncanny number of similarities in the conditions that cause their activation, some have considered these pancreatic and hepatic oval cells to be one in the same cell type. The hepatic oval cells have been usually thought to be the progeny of a hepatic stem cell, native to the liver. Recently, however, we as well as others have obtained clear evidence that in the rat hepatic oval cells, or at least a fraction of them, can be derive from a precursor cell of bone marrow origin. Perhaps, the pancreatic oval cells, which lie in the ductular region and gives rise to the different epithelial cell types may in fact be derived from an extra-pancreatic source (i.e. bone marrow). Having been the first to show that oval cells can be derived from an extra-hepatic source we now have the technology to answer the question of cell of origin through the use of sex mismatched bone marrow transplants. The goals of this project are to identify and phenotypically characterize the bone marrow-associated cell that can act as a progenitor of pancreatic oval cells. Towards achievement of these goals, we will perform a series of studies aimed at to test the hypothesis that bone marrow derived stem cells participate in the regeneration process in the injured rat pancreas. (Specific Aim I); and to establish whether the CD- 34+ or CD-34- sub-population of bone marrow cells contains the oval cell progenitor and produces the highest percentage of bone marrow derived pancreatic cells (Specific Aim II). It is anticipated, with confidence, that performance of the proposed studies will yield new and significant data about the overall biology of pancreatic oval cells, and the basic phenotype and properties of their bone marrow precursor. The same data could potentially provide a valuable resource for future tissue engineering and cell therapy technique interventions in pancreatic regeneration.
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