Insulin expression and C-peptide in type 1 diabetes subjects implanted with stem cell-derived pancreatic endoderm cells in an encapsulation device

Shapiro, A. M. James; Thompson, David M.; Donner, Thomas; Bellin, Melena D.; Hsueh, Willa A.; Pettus, Jeremy; Wilensky, Jon; Daniels, Mark; Wang, Richard M.; Brandon, Eugene P.; Jaiman, Manasi S.; Kroon, Evert; D’Amour, Kevin A.; Foyt, Howard L.

doi:10.1016/j.xcrm.2021.100466

Cited by 191 publications

(142 citation statements)

References 19 publications

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“…In a subsequent trial, portals that permitted vascular ingrowth were added to the device, but these also conferred access to the immune system, which made induction and maintenance immunotherapy necessary. Recently, Shapiro and colleagues reported findings from a multicenter trial that included 17 patients ( 7 ), and Ramzy and colleagues reported on a single-center study of 15 individuals that focused on clinical measures including sequential meal studies ( 8 ).…”

Section: Recent Progress In Cell-based Therapies For Diabetesmentioning

confidence: 99%

Reversing type 1 diabetes with stem cell–derived islets: a step closer to the dream?

Butler¹,

Gale²

2022

Journal of Clinical Investigation

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Section: Recent Progress In Cell-based Therapies For Diabetesmentioning

confidence: 99%

Reversing type 1 diabetes with stem cell–derived islets: a step closer to the dream?

Butler¹,

Gale²

2022

Journal of Clinical Investigation

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“…Transplantation of ESC-derived PPs into mice was far superior to in vitro differentiation, with respect to obtaining glucose-responsive stem cell-derived β cells (SC-β) [ 97 , 98 , 99 ]. Currently, there are ongoing clinical trials based on the use of encapsulated hESC-derived PPs as cell replacement therapy for T1D, with first-in-human phase 1/2 results already disseminated [ 100 , 101 ].…”

Section: Models To Study the Genetic Basis Of β Cell Dysfunctionmentioning

confidence: 99%

Stem Cell-Derived β Cells: A Versatile Research Platform to Interrogate the Genetic Basis of β Cell Dysfunction

Bartolomé

2022

IJMS

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Pancreatic β cell dysfunction is a central component of diabetes progression. During the last decades, the genetic basis of several monogenic forms of diabetes has been recognized. Genome-wide association studies (GWAS) have also facilitated the identification of common genetic variants associated with an increased risk of diabetes. These studies highlight the importance of impaired β cell function in all forms of diabetes. However, how most of these risk variants confer disease risk, remains unanswered. Understanding the specific contribution of genetic variants and the precise role of their molecular effectors is the next step toward developing treatments that target β cell dysfunction in the era of personalized medicine. Protocols that allow derivation of β cells from pluripotent stem cells, represent a powerful research tool that allows modeling of human development and versatile experimental designs that can be used to shed some light on diabetes pathophysiology. This article reviews different models to study the genetic basis of β cell dysfunction, focusing on the recent advances made possible by stem cell applications in the field of diabetes research.

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“…Mature glucose-responsive β-like cells that are functionally equivalent to cadaveric islets can be obtained by different protocols (Sambathkumar et al, 2018; Sui et al, 2018; Veres et al, 2019). Two studies reporting interim data from ongoing first-in-human iPSCs-based transplants showed restoration of meal-induced C-peptide response for up to 1 year after implantation of iPSCs-derived islet cells, providing proof-of-concept for this approach (Ramzy et al, 2021; Shapiro et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Triple Notch/Tgfβ/FoxO1 blockade converts multiple intestinal sub-lineages into β-like cells and lowers glycemia in diabetic animals

Wang

Kuo

et al. 2022

Preprint

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Insulin is the essential treatment of Type 1 (T1D) and is often used in Type 2 Diabetes. For nearly five decades, efforts have been focused on replenishing β-cells in T1D patients as a more durable treatment. Gut endocrine cells can be converted into insulin-producing cells, but their numbers are limited. In this study we report that insulin-immunoreactive cells with Paneth/goblet cell features are present in human fetal intestine, in addition to enteroendocrine cells. Accordingly, lineage tracing experiments show that, besides enterochromaffin cells, the Paneth/goblet lineage can undergo conversion to the insulin lineage upon genetic or pharmacologic Foxo1 ablation in mice. We leveraged these data to design a screening platform in organoids to accurately quantitate β-like cell reprogramming and fine-tune a combination treatment to increase the efficiency of the conversion process by expanding the intestinal secretory lineage. We identified a triple blockade of FoxO1, Notch, and Tgfβ that, when tested in insulin-deficient diabetic animals resulted in a near-normalization of glucose levels, associated with the appearance of gut insulin-producing cells. The findings illustrate a therapeutic approach to replace insulin treatment in diabetes.

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Insulin expression and C-peptide in type 1 diabetes subjects implanted with stem cell-derived pancreatic endoderm cells in an encapsulation device

Cited by 191 publications

References 19 publications

Reversing type 1 diabetes with stem cell–derived islets: a step closer to the dream?

Reversing type 1 diabetes with stem cell–derived islets: a step closer to the dream?

Stem Cell-Derived β Cells: A Versatile Research Platform to Interrogate the Genetic Basis of β Cell Dysfunction

Triple Notch/Tgfβ/FoxO1 blockade converts multiple intestinal sub-lineages into β-like cells and lowers glycemia in diabetic animals

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