Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The efficacy of islet transplantation for diabetes treatment suffers from lack of cadaver-derived islets, islet necrosis and long transfer times prior to transplantation. Here, we developed a method for culturing mouse and human islets in vitro on α5-laminins, which are natural components of islet basement membranes. Adhering islets spread to form layers of 1-3 cells in thickness and remained normoxic and functional for at least 7 days in culture. In contrast, spherical islets kept in suspension developed hypoxia and central necrosis within 16 h. Transplantation of 110-150 mouse islets cultured on α5-laminin-coated polydimethylsiloxane membranes for 3-7 days normalized blood glucose already within 3 days in mice with streptozotocin-induced diabetes. RNA-sequencing of isolated and cultured mouse islets provided further evidence for the adhesion and spreading achieved with α5-laminin. Our results suggest that use of such in vitro expanded islets may significantly enhance the efficacy of islet transplantation treatment for diabetes.
Date Issued
2018-09-01
Date Acceptance
2018-03-22
Citation
Matrix Biology, 2018, 70, pp.5-19
ISSN
0945-053X
Publisher
Elsevier
Start Page
5
End Page
19
Journal / Book Title
Matrix Biology
Volume
70
Copyright Statement
© 2018 The Authors. Published by Elsevier B.V. This is a open access article available under a CC-BY 4.0 (https://creativecommons.org/licenses/by/4.0/)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29601863
PII: S0945-053X(18)30052-0
Subjects
Diabetes
Islet
Laminin
Pancreatic
Transplantation
β-cell
Publication Status
Published
Coverage Spatial
Netherlands
Date Publish Online
2018-03-27