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A vascularized 3D model of the human pancreatic islet for ex vivo study of immune cell-islet interaction

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Item Type:Article
Title:A vascularized 3D model of the human pancreatic islet for ex vivo study of immune cell-islet interaction
Creators Name:Bender, R.H.F. and O'Donnell, B.T. and Shergill, B. and Pham, B.Q. and Tahmouresie, S. and Sanchez, C.N. and Juat, D.J. and Hatch, M.M.S. and Shirure, V.S. and Wortham, M. and Nguyen-Ngoc, K.V. and Jun, Y. and Gaetani, R. and Christman, K.L. and Teyton, L. and George, S.C. and Sander, M. and Hughes, C.C.W.
Abstract:Insulin is an essential regulator of blood glucose homeostasis that is produced exclusively by β cells within the pancreatic islets of healthy individuals. In those affected by diabetes, immune inflammation, damage, and destruction of islet β cells leads to insulin deficiency and hyperglycemia. Current efforts to understand the mechanisms underlying β cell damage in diabetes rely on in vitro-cultured cadaveric islets. However, isolation of these islets involves removal of crucial matrix and vasculature that supports islets in the intact pancreas. Unsurprisingly, these islets demonstrate reduced functionality over time in standard culture conditions, thereby limiting their value for understanding native islet biology. Leveraging a novel, vascularized micro-organ (VMO) approach, we have recapitulated elements of the native pancreas by incorporating isolated human islets within a three-dimensional matrix nourished by living, perfusable blood vessels. Importantly, these islets show long-term viability and maintain robust glucose-stimulated insulin responses. Furthermore, vessel-mediated delivery of immune cells to these tissues provides a model to assess islet-immune cell interactions and subsequent islet killing - key steps in type 1 diabetes pathogenesis. Together, these results establish the islet-VMO as a novel, ex vivo platform for studying human islet biology in both health and disease.&#xD.
Keywords:Microphysiological Systems, Organ-on-a-Chip, Diabetes, Islet Biology, Glucose-Stimulated, Insulin Secretion
Publisher:Institute of Physics Publishing (IOP)
Page Range:025001
Date:11 January 2024
Official Publication:https://doi.org/10.1088/1758-5090/ad17d0
PubMed:View item in PubMed

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