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Matrix Biol. 2018 Sep;70:5-19. doi: 10.1016/j.matbio.2018.03.018. Epub 2018 Mar 27.

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

Author information

1
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore.
2
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
3
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore; Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
4
Division of Biomaterials and Regenerative Medicine, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
5
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
6
Division of Biomaterials and Regenerative Medicine, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Department of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
7
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore; Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Electronic address: karl.tryggvason@duke-nus.edu.sg.

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.

KEYWORDS:

Diabetes; Islet; Laminin; Pancreatic; Transplantation; β-cell

PMID:
29601863
DOI:
10.1016/j.matbio.2018.03.018
[Indexed for MEDLINE]
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