Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration.

Citation
Saunders, D. C., et al. “Coordinated Interactions Between Endothelial Cells And Macrophages In The Islet Microenvironment Promote Β Cell Regeneration.”. Npj Regenerative Medicine, p. 22.
Center Vanderbilt University
Author Diane C Saunders, Kristie I Aamodt, Tiffany M Richardson, Alexander J Hopkirk, Radhika Aramandla, Greg Poffenberger, Regina Jenkins, David K Flaherty, Nripesh Prasad, Shawn E Levy, Alvin C Powers, Marcela Brissova
Abstract

Endogenous β cell regeneration could alleviate diabetes, but proliferative stimuli within the islet microenvironment are incompletely understood. We previously found that β cell recovery following hypervascularization-induced β cell loss involves interactions with endothelial cells (ECs) and macrophages (MΦs). Here we show that proliferative ECs modulate MΦ infiltration and phenotype during β cell loss, and recruited MΦs are essential for β cell recovery. Furthermore, VEGFR2 inactivation in quiescent ECs accelerates islet vascular regression during β cell recovery and leads to increased β cell proliferation without changes in MΦ phenotype or number. Transcriptome analysis of β cells, ECs, and MΦs reveals that β cell proliferation coincides with elevated expression of extracellular matrix remodeling molecules and growth factors likely driving activation of proliferative signaling pathways in β cells. Collectively, these findings suggest a new β cell regeneration paradigm whereby coordinated interactions between intra-islet MΦs, ECs, and extracellular matrix mediate β cell self-renewal.

Year of Publication
2021
Journal
NPJ Regenerative medicine
Volume
6
Issue
1
Number of Pages
22
Date Published
04/2021
ISSN Number
2057-3995
DOI
10.1038/s41536-021-00129-z
Alternate Journal
NPJ Regen Med
PMID
33824346