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Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice

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Title: Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice
Authors: Sigmundsson, K
Ojala, JRM
Öhman, MK
Österholm, A-M
Moreno-Moral, A
Domogatskaya, A
Chong, LY
Sun, Y
Chai, X
Steele, JAM
George, B
Patarroyo, M
Nilsson, A-S
Rodin, S
Ghosh, S
Stevens, MM
Petretto, E
Tryggvason, K
Item 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.
Issue Date: 1-Sep-2018
Date of Acceptance: 22-Mar-2018
URI: http://hdl.handle.net/10044/1/59225
DOI: https://dx.doi.org/10.1016/j.matbio.2018.03.018
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/)
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Diabetes
Laminin
Pancreatic
Islet
Transplantation
beta-cell
BETA-CELL PROLIFERATION
BASEMENT-MEMBRANE
GENE-EXPRESSION
STREPTOZOTOCIN
SHEETS
INHIBITION
MELLITUS
LAMININS
SURVIVAL
INTEGRIN
β-cell
06 Biological Sciences
Publication Status: Published
Conference Place: Netherlands
Open Access location: https://www.sciencedirect.com/science/article/pii/S0945053X18300520
Online Publication Date: 2018-03-27
Appears in Collections:Faculty of Engineering
Materials
Clinical Sciences
Molecular Sciences
Faculty of Medicine
Faculty of Natural Sciences



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