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