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

Stock AA, Manzoli V, De Toni T, Abreu MM, Poh YC, Ye L, Roose A, Pagliuca FW, Thanos C, Ricordi C, Tomei AA

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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.

Abstract of "Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes" by Stock AA, Manzoli V, De Toni T et al., https://doi.org/10.1016/j.stemcr.2019.11.004, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.

Record

Archive ID
doi:10.1016/j.stemcr.2019.11.004
Published
Dec 12, 2019
Venue
Stem cell reports
DOI
10.1016/j.stemcr.2019.11.004
PubMed
31839542
PMC
PMC6962554
License
CC-BY
Provenance
europepmc

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