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Learn MorePancreatic islet endocrine cell and endothelial cell (EC) interactions mediated by vascular endothelial growth factor-A (VEGF-A) signaling are important for islet endocrine cell differentiation and the formation of highly vascularized islets. To dissect how VEGF-A signaling modulates intra-islet vasculature and innervation, islet microenvironment, and cell mass, we transiently increased VEGF-A production by cells. VEGF-A induction dramatically increased the number of intra-islet ECs but led to cell loss. After withdrawal of the VEGF-A stimulus, cell mass, function, and islet structure normalized as a result of a robust, but transient, burst in proliferation of pre-existing cells. Bone marrow-derived macrophages (Ms) recruited to the site of cell injury were crucial for the cell proliferation, which was independent of pancreatic location and circulating factors such as glucose. Identification of the signals responsible for the proliferation of adult, terminally differentiated cells will improve strategies aimed at cell regeneration and expansion. SOURCE: Alvin,C,Powers Vanderbilt University Medical Center
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