Neonatal pancreatic pericytes support β-cell proliferation

Objective: The maintenance and expansion of beta-cell mass rely on their proliferation, which reaches its peak in the neonatal stage. beta-cell proliferation was found to rely on cells of the islet microenvironment. We hypothesized that pericytes, which are components of the islet vasculature, support neonatal fl-cell proliferation. Methods: To test our hypothesis, we combined in vivo and in vitro approaches. Briefly, we used a Diphtheria toxin-based transgenic mouse system to specifically deplete neonatal pancreatic pericytes in vivo. We further cultured neonatal pericytes isolated from the neonatal pancreas and combined the use of a beta-cell line and primary cultured mouse beta-cells. Results: Our findings indicate that neonatal pancreatic pericytes are required and sufficient for beta-cell proliferation. We observed impaired proliferation of neonatal beta-cells upon in vivo depletion of pancreatic pericytes. Furthermore, exposure to pericyte-conditioned medium stimulated proliferation in cultured beta-cells. Conclusions: This study introduces pancreatic pericytes as regulators of neonatal beta-cell proliferation. In addition to advancing current understanding of the physiological beta-cell replication process, these findings could facilitate the development of protocols aimed at expending these cells as a potential cure for diabetes. (C) 2017 The Authors. Published by Elsevier GmbH.