Neonatal pancreatic pericytes support β-cell proliferation

Alona Epshtein, Eleonor Rachi, Lina Sakhneny, Shani Mizrachi, Daria Baer, Limor Landsman

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The maintenance and expansion of β-cell mass rely on their proliferation, which reaches its peak in the neonatal stage. β-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 β-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 β-cell line and primary cultured mouse β-cells. Results: Our findings indicate that neonatal pancreatic pericytes are required and sufficient for β-cell proliferation. We observed impaired proliferation of neonatal β-cells upon in vivo depletion of pancreatic pericytes. Furthermore, exposure to pericyte-conditioned medium stimulated proliferation in cultured β-cells. Conclusions: This study introduces pancreatic pericytes as regulators of neonatal β-cell proliferation. In addition to advancing current understanding of the physiological β-cell replication process, these findings could facilitate the development of protocols aimed at expending these cells as a potential cure for diabetes.

Original languageEnglish
Pages (from-to)1330-1338
Number of pages9
JournalMolecular Metabolism
Volume6
Issue number10
DOIs
StatePublished - Oct 2017

Keywords

  • Beta-cells
  • Islets
  • Neonatal pancreas
  • Pericytes
  • Vasculature

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