Peribiliary Glands as a Niche of Extrapancreatic Precursors Yielding Insulin-Producing Cells in Experimental and Human Diabetes

• DOI: 10.1002/stem.2311
• Publication Date: 2016-02-06T10:58:09Z
• Authors: Guido Carpino; Rosa Puca; Vincenzo Cardinale; Anastasia Renzi; Gaia Scafetta; Lorenzo Nevi; Massimo Rossi; Pasquale B. Berloco; Stefano Ginanni C...; Lola M. Reid; Marella Maroder; Eugenio Gaudio; Domenico Alvaro
• Keywords: Male; 0301 basic medicine; Stem Cells; Cell Differentiation; Biliary tree; Endoderm; Peribiliary gland; Regeneration; Stem cell; Streptozotocin; Animals; Biliary Tract; Cell Compartmentation; Cell Differentiation; Cell Proliferation; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin; Insulin-Secreting Cells; Male; Mice, Inbred C57BL; Stem Cells; Streptozocin; Stem Cell Niche; Streptozocin; Cell Compartmentation; Diabetes Mellitus, Experimental; Mice, Inbred C57BL; 03 medical and health sciences; Glucose; Diabetes Mellitus, Type 2; Insulin-Secreting Cells; biliary tree; endoderm; peribiliary gland; regeneration; stem cell; streptozotocin; Animals; Humans; Insulin; Stem Cell Niche; Biliary Tract; Cell Proliferation

Abstract Peribiliary glands (PBGs) are niches in the biliary tree and containing heterogeneous endodermal stem/progenitors cells that can differentiate, vitro vivo, toward pancreatic islets. The aim of this study was to evaluate, experimental human diabetes, proliferation PBGs differentiation stem/progenitor (BTSCs) insulin-producing cells. Diabetes generated mice by intraperitoneal injection a single dose 200 mg/kg (N = 12) or 120 streptozotocin. Liver, pancreas, extrahepatic trees were en bloc dissected examined. Cells proliferated their greatest hepatopancreatic ampulla, inversely correlated with islet area. In rodents, cell characterized expansion Sox9-positive gave rise Insulin-producing located mostly portion closest duodenum, appearance associated upregulation MafA Gli1 gene expression. patients type 2 at level ampulla contained showing signs fate commitment. vitro, high glucose concentrations induced BTSCs cultures beta fates. respond diabetes towards indicating PBG may rescue impairment diabetes. These findings offer important implications for pathophysiology complications disease.