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Stem Cell Reports. 2020 Jan 14;14(1):91-104. doi: 10.1016/j.stemcr.2019.11.004. Epub 2019 Dec 12.

Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes.

Author information

1
Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10(th) Avenue, Miami, FL 33136, USA; Department of Biomedical Engineering, University of Miami, Miami, FL 33146, USA.
2
Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10(th) Avenue, Miami, FL 33136, USA.
3
Semma Therapeutics, Inc., Cambridge, MA 02142, USA.
4
Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10(th) Avenue, Miami, FL 33136, USA; Department of Biomedical Engineering, University of Miami, Miami, FL 33146, USA; Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
5
Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10(th) Avenue, Miami, FL 33136, USA; Department of Biomedical Engineering, University of Miami, Miami, FL 33146, USA; Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: atomei@miami.edu.

Abstract

The scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Transplantation of encapsulated stem cell-derived islets (SC islets) might extend the applicability of islet transplantation to a larger cohort of patients. Transplantation of conformal-coated islets into a confined well-vascularized site allows long-term diabetes reversal in fully MHC-mismatched diabetic mice without immunosuppression. Here, we demonstrated that human SC islets reaggregated from cryopreserved cells display glucose-stimulated insulin secretion in vitro. Importantly, we showed that conformally coated SC islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. Overall, these results provide support for further evaluation of safety and efficacy of conformal-coated SC islets in larger species.

KEYWORDS:

Type 1 Diabetes; alginate; conformal coating; encapsulation; insulin; islet transplantation; polyethylene glycol; stem cell-derived islets; thiol-ene click chemistry; β cells

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