Label-Retaining Cells in the Rat Pancreas

Label-Retaining Cells in the Rat Pancreas Location and Differentiation Potential in Vitro Bertrand Duvillié 1 , Myriam Attali 1 , Virginie Aiello 1 , Eric Quemeneur 2 and Raphael Scharfmann 1 1 INSERM U457 and E0363, Hospital R. Debré, Paris, France 2 CEA, Bagnols sur Cèze, France Address correspondence and reprint requests to Bertrand Duvillié, INSERM U457, Hospital R. Debre, 48 Bd Serurier, 75019 Paris, France. E-mail: duvillie{at}idf.inserm.fr Abstract Islets of Langerhans are micro-organs scattered throughout the pancreas that contain insulin-producing cells, called β-cells. Although new light has been recently shed on β-cell development, information on the phenotype and location of β-stem cells remains scarce. Here, we provide evidence that β-stem cells are slow-cycling cells located within and around the islets of Langerhans. First, using a bromodeoxyuridine (BrdU) pulse/chase approach, we detected BrdU-retaining cells in vivo in the islet area of rat pancreata. These cells were negative for endocrine markers but expressed Pdx1, a marker for pancreatic stem cells. Next, using an in vitro model that mimicked endocrine cell development, we found that BrdU-retaining cells were capable of differentiating into β-cells. Taken together, these observations demonstrate that BrdU retention is a property of β-stem cells. BrdU, bromodeoxyuridine FGF7, fibroblast growth factor 7 HBSS, Hank’s balanced salt solution Footnotes Accepted May 12, 2003. Received March 12, 2003. DIABETES