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Engineering islets from stem cells for advanced therapies of diabetes

Abstract

Diabetes mellitus is a metabolic disorder that affects more than 460 million people worldwide. Type 1 diabetes (T1D) is caused by autoimmune destruction of β-cells, whereas type 2 diabetes (T2D) is caused by a hostile metabolic environment that leads to β-cell exhaustion and dysfunction. Currently, first-line medications treat the symptomatic insulin resistance and hyperglycaemia, but do not prevent the progressive decline of β-cell mass and function. Thus, advanced therapies need to be developed that either protect or regenerate endogenous β-cell mass early in disease progression or replace lost β-cells with stem cell-derived β-like cells or engineered islet-like clusters. In this Review, we discuss the state of the art of stem cell differentiation and islet engineering, reflect on current and future challenges in the area and highlight the potential for cell replacement therapies, disease modelling and drug development using these cells. These efforts in stem cell and regenerative medicine will lay the foundations for future biomedical breakthroughs and potentially curative treatments for diabetes.

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Fig. 1: Approaches to generate pancreatic human islets.
Fig. 2: Translation of the in vivo differentiation of islets of Langerhans to a dish.
Fig. 3: Potency assay for SC-islets to predict function after transplantation.

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Acknowledgements

The authors apologize to all colleagues for not mentioning their work in this Review due to space constraints. The authors are thankful for funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement ISLET number 874839. This work was further supported by the German Federal Ministry of Education and Research (BMBF) (PancChip 01EK1607A and e-ISLET 031L0251), the German Center for Diabetes Research (DZD e.V.), the Helmholtz Association and the Technical University Munich. They would like to thank C. Daniel for valuable comments on the manuscript.

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Siehler, J., Blöchinger, A.K., Meier, M. et al. Engineering islets from stem cells for advanced therapies of diabetes. Nat Rev Drug Discov 20, 920–940 (2021). https://doi.org/10.1038/s41573-021-00262-w

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