Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells

  title={Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells},
  author={Alireza Rezania and Jennifer E. Bruin and Payal Arora and Allison Rubin and Irina Batushansky and Ali Asadi and Shannon M. O’Dwyer and Nina Quiskamp and Majid Mojibian and Tobias Albrecht and Yu Hsuan Carol Yang and James D. Johnson and Timothy J. Kieffer},
  journal={Nature Biotechnology},
Transplantation of pancreatic progenitors or insulin-secreting cells derived from human embryonic stem cells (hESCs) has been proposed as a therapy for diabetes. We describe a seven-stage protocol that efficiently converts hESCs into insulin-producing cells. Stage (S) 7 cells expressed key markers of mature pancreatic beta cells, including MAFA, and displayed glucose-stimulated insulin secretion similar to that of human islets during static incubations in vitro. Additional characterization… 

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A detailed protocol for the generation of pancreatic progenitor cells from human pluripotent stem cells (hPSCs) is described, providing methods for the directed differentiation as well as the characterization of pancreas-related cells and lineage intermediates by immunofluorescence staining and flow cytometry.

Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.

A thorough evaluation of SC-islet maturation highlights their advanced degree of functionality and supports their use in further efforts to understand and combat diabetes.

Sex Differences in Maturation of Human Embryonic Stem Cell–Derived &bgr; Cells in Mice

Pancreatic progenitors derived from human embryonic stem cells (hESCs) are now in clinical trials for insulin replacement in patients with type 1 diabetes and data indicate that the host sex may impact the maturation of hESC-derived cells in vivo and that this effect can be minimized by more advanced differentiation of the cells before implantation.



Maturation of Human Embryonic Stem Cell–Derived Pancreatic Progenitors Into Functional Islets Capable of Treating Pre-existing Diabetes in Mice

A protocol to efficiently differentiate commercially available human embryonic stem cells in vitro into a highly enriched PDX1+ pancreatic progenitor cell population that further develops in vivo to mature pancreatic endocrine cells supports the feasibility of using differentiated hESCs as an alternative to cadaveric islets for treating patients with diabetes.

Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo

It is shown that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice, and it is demonstrated that implantation of hES cell–derived pancreaticEndoderm protects against streptozotocin-induced hyperglycemia.

Production of pancreatic hormone–expressing endocrine cells from human embryonic stem cells

A differentiation process that converts human embryonic stem cells to endocrine cells capable of synthesizing the pancreatic hormones insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin is developed.

Production of Functional Glucagon-Secreting α-Cells From Human Embryonic Stem Cells

Results indicate that fully differentiated pancreatic endocrine cells can be created via stepwise differentiation of hES cells, and these cells may serve as a useful screening tool for the identification of compounds that modulate glucagon secretion as well as those that promote the transdifferentiation of α-cells to β-cells.

Maturation and function of human embryonic stem cell-derived pancreatic progenitors in macroencapsulation devices following transplant into mice

An improved differentiation protocol was developed that aimed to prevent the formation of off-target mesoderm tissue following transplantation and efficient differentiation of hESC-derived pancreatic endocrine cells can occur in a macroencapsulation device, yielding glucose-responsive insulin-producing cells capable of reversing diabetes.

A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells

A tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry is developed.

A small molecule that directs differentiation of human ESCs into the pancreatic lineage.

A chemical screening platform to investigate human ESC differentiation is described and the generation of a cell population that is a key milepost on the path to making beta cells is demonstrated.

The functional and molecular characterisation of human embryonic stem cell-derived insulin-positive cells compared with adult pancreatic beta cells

insulin+ cells were heterogeneous, a fact that translated into important functional differences within this population, and can be purified from differentiated hESCs, providing a superior source of insulin-producing cells.