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Pancreatic Stem Cells

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.

Related Publications

Smukler, S., Arntfield, M., Bikopoulos, G., Seaberg, R., Dai, F., Lee, S., Wheeler, M., and van der Kooy, D. The adult mouse and human pancreas contain multipotential stem cells that express insulin. Cell Stem Cell. 8 (2011) 281-293. (smukler...2011...)

Arntfield, M.E., and van der Kooy, D. Evolution of the β-cell: How the pancreas borrowed from the brain. Bioessays. 16 (2011) 582-7. (arntfield...2011...)

Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB, Korbutt G, van der Kooy D.Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol. 2004 Sep;22(9):1115-24. in .pdf ...:


**photo credit: Simon Smukler photo depicts differentiated cell progeny derived from a single pancreas-derived precursor cell. The green colour represents labeling of insulin (pancreatic beta cells) and the red colour represents labeling of a neuron-specific marker. The blue colour shows the nuclei of all the cells present in the field. From Seaberg, et al, Nature Biotechnology, 2004 Sep;22(9):1115-24.