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

Insulin is an essential regulator of blood glucose homeostasis that is produced exclusively by cells within the pancreatic islets of healthy individuals. In those affected by diabetes, immune inflammation, damage, and destruction of islet cells leads to insulin deficiency and hyperglycemia. Current...

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Bibliographic Details
Published in:	Biofabrication Vol. 16; no. 2
Main Authors:	Bender, R Hugh F, O'Donnell, Benjamen T, Shergill, Bhupinder, Pham, Brittany Q, Tahmouresie, Sima, Sanchez, Celeste N, Juat, Damie J, Hatch, Michaela M S, Shirure, Venktesh S, Wortham, Matthew, Nguyen-Ngoc, Kim-Vy, Jun, Yesl, Gaetani, Roberto, Christman, Karen L, Teyton, Luc, George, Steven C, Sander, Maike, Hughes, Christopher C W
Format:	Journal Article
Language:	English
Published:	England 01-04-2024
Subjects:	Diabetes Mellitus - metabolism Glucose - metabolism Humans Insulin - metabolism Islets of Langerhans Islets of Langerhans Transplantation islet biology organ-on-a-chip glucose-stimulated insulin secretion microphysiological systems diabetes
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Summary:	Insulin is an essential regulator of blood glucose homeostasis that is produced exclusively by cells within the pancreatic islets of healthy individuals. In those affected by diabetes, immune inflammation, damage, and destruction of islet cells leads to insulin deficiency and hyperglycemia. Current efforts to understand the mechanisms underlying cell damage in diabetes rely on -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, platform for studying human islet biology in both health and disease.
ISSN:	1758-5090
DOI:	10.1088/1758-5090/ad17d0