We have isolated a rare cell from the adult mouse pancreas (.01%) that can show extensive proliferation under completely defined conditions in vitro (Seaberg et al, 2004).  Each single, adult pancreatic multipotent precursor (PMP) cell produces progeny from two separate organ lineages (and only those lineages): first, exocrine and endocrine pancreatic lineage cells (including B-like cells) and second, neurons and glial cells.  We suggest that in vivo PMPs only make pancreatic lineage cells, but in vitro the expression of a toolbox of transcription factors that are important in both pancreatic and neural development permits the PMPs to make neural cells as well.  We hypothesize that these cells may comprise a population of adult mammalian pancreatic stem cells, which might in the future be employed in treating type 1 diabetics.

We look at the  in vitro self-renewal and expansion of the pancreatic stem cell colonies through the expression of candidate molecules such as Notch in vivo and Wnt, as well as concentrations and media components.  This is particularly important if we are to maximize the number of cells available for treatment in mouse diabetic models (see 3rd aim below) and eventually in humans.  Thus, we will undertake small molecule screens for compounds that increase in the survival and expansion through symmetrical cell divisions of pancreatic stem cells and increase differentiation of insulin producing beta cell progeny of pancreatic stem cells.  Second, an apparent adult human pancreatic stem cell with properties similar to that of the adult mouse pancreatic stem cell will be characterized in detail.  Third, the in vitro PMP colonies will be transplanted into a diabetic mouse model to test for recovery of blood sugar levels.