Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes.

@article{Ramzy2021ImplantedPS,
  title={Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes.},
  author={Adam Ramzy and D. M. Thompson and Kirsten A. Ward-Hartstonge and Sabine M. Ivison and Laura Cook and Rosa V. Garcia and Jackson Loyal and Peter T. W. Kim and Garth L. Warnock and Megan K. Levings and Timothy J. Kieffer},
  journal={Cell stem cell},
  year={2021},
  volume={28 12},
  pages={
          2047-2061.e5
        }
}

Stem-cell derived pancreatic endoderm cells in the treatment of T1DM

  • C. Greenhill
  • Medicine, Biology
    Nature Reviews Endocrinology
  • 2021
TLDR
Preliminary findings from an ongoing phase I/II trial in which patients with T1DM received implants of stem-cell derived pancreatic endoderm cells within an encapsulation device named PEC-Direct report the first reported evidence of meal-regulated insulin secretion from a stem cell-based treatment for T1 DM.

Stem cells differentiation into insulin-producing cells (IPCs): recent advances and current challenges

TLDR
Research efforts have been directed to the final steps of in vitro differentiation, aiming at production of functional and mature β -cells and integration of interdisciplinary fields to generate efficient cell therapy strategies capable of reversing the clinical outcome of T1D.

Strategies to Improve the Safety of iPSC-Derived β Cells for β Cell Replacement in Diabetes

TLDR
Four approaches to increase the safety of PSC-derived β cells are discussed: reprogramming of somatic cells into induced PSC, selection of pure differentiated pancreatic cells, depletion of contaminant PSC in the final cell product, and control or destruction of tumorigenic cells with engineered suicide genes.

Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation

TLDR
It is suggested that short-term in vitro treatment with clinical-grade anti-CD30, targeting residual undifferentiated cells, eliminates the tumorigenicity of iPSC-derived β cells, potentially providing enhanced safety for i PSC-based β cell replacement therapy in clinical scenarios.

The progress of pluripotent stem cell-derived pancreatic β-cells regeneration for diabetic therapy

TLDR
The current progress and protocols of generating pancreatic β-cells from human PSCs are summarized and some challenges and future perspectives of human P SCs treatments for diabetes are discussed.

Stem Cell-Derived Islets for Type 2 Diabetes

TLDR
A perspective review will provide insight into the efficacy of hPSC-derived human islets for treating and understanding type 2 diabetes, and the use of stem cells for the modeling of T2D and the potential use of hPD-derived islet transplantation for treating T2d.

Manufacturing clinical‐grade human induced pluripotent stem cell‐derived beta cells for diabetes treatment

TLDR
This review focuses on the key processes and guidelines for clinical translation of human induced pluripotent stem cell (hiPSC)‐derived β cells for diabetes cell therapy and key considerations of manufacturing clinical‐grade hiPSCs.

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

TLDR
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.

Initial Clinical Evaluation of VC-01TM Combination Product—A Stem Cell–Derived Islet Replacement for Type 1 Diabetes (T1D)

TLDR
Preliminary results demonstrate the immune-protective nature of the encapsulation device and safety of this human stem cell-derived product, but also indicate the ongoing requirement for optimization of the host response to device materials.

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

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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.

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Sp spontaneous in vitro differentiation that included the generation of cells with characteristics of insulin-producing beta-cells is observed, validating the hES cell model system as a potential basis for enrichment of human beta- cells or their precursors, as a possible future source for cell replacement therapy in diabetes.

Stem Cell Therapy for Diabetes: Beta Cells versus Pancreatic Progenitors

TLDR
The co-generation of functionally relevant islet cell subpopulations and structural properties contributing to the glucose responsiveness of beta cells, as well as the available encapsulation technology for these cells are addressed.

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TLDR
Although S7 cells are not fully equivalent to mature beta cells, their capacity for glucose-responsive insulin secretion and rapid reversal of diabetes in vivo makes them a promising alternative to pancreatic progenitor cells or cadaveric islets for the treatment of diabetes.

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

TLDR
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.
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