Beta-cell replacement therapy offers

a cure for diabetes, but this is limited by the lack of readily

available supply of cells. Our goal is generate enough beta-cells to meet the

demand for transplantation, by proliferating both mature

beta-cells and pancreatic progenitor cells prior to

differentiation into beta-cells.

Pancreatic progenitor cell growth has

previously been shown to depend on Fibroblast Growth Factor (FGF) from the

mesenchyme. We have identified Wnt7b as a physiological

regulator of pancreatic progenitor cell growth. Wnt7b is present

in the pancreatic progenitor cells, and not the pancreatic

mesenchyme. Genetic deletion of Wnt7b causes

stunted pancreatic growth in mouse embryos. In these embryos, the

mass of the pancreas is reduced to 57% of wild type, but differentiation

proceeds normally (Figure 1). Loss of Wnt7b abolishes canonical Wnt signaling

in the pancreas leading to a reduction in the proliferation rate of pancreatic

progenitor cells by 40%.

Adult pancreatic exocrine cells can assume a progenitor state in vitro. As

FGF had previously been shown to promote pancreatic progenitor cell

growth, we tested the effect of FGF

and Wnt signaling on the growth of adult-derived

pancreatic progenitor cells prior to differentiation into beta-cells.

Wnt alone does not produce a significant effect, while

FGF alone increases pancreatic progenitor cell growth slightly

(Figure 2 C). However FGF and Wnt signaling together induce a pronounced

increase in pancreatic progenitor cell growth, indicating a synergistic effect

between these two pathways in pancreatic progenitor cell growth (Figure 2 D). We are

currently testing the effect of Wnt signaling in promoting the growth of adult

pancreatic beta-cells in vitro.

CITATION INFORMATION: Afelik S, Yonan N, Pool B, Jensen J, Oberholzer J. FGF and Wnt Signaling in Pancreatic Progenitor and Beta-Cell Growth. Am J Transplant. 2016;16 (suppl 3).

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