Hedgehog Signaling during Expansion of Human Pancreatic Islet-Derived Precursors


Address for correspondence: Francesco Dotta, Diabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, Policlinico “Le Scotte,” viale Bracci 18, 53100 Siena, Italy. Voice: +39 0577 586269; fax: +39 0577 586186. francesco.dotta@alice.it


A detailed understanding of the molecular process involved in the proliferation of pancreatic precursor cells would provide key elements for developing new therapeutic strategies to cure type 1 diabetes. In the present study we investigated the potential involvement of hedgehog signaling in proliferating human pancreatic islet-derived mesenchymal (hPIDM) cells, a population of cells that can be successfully expanded and induced to differentiate into an insulin-secreting phenotype. Here we report that in these precursor cells a hedgehog signaling pathway is activated, as shown by Gli1 expression, and that a dose-dependent inhibition of such a pathway by cyclopamine results in a significant reduction of cell proliferation.