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Related Experiment Video

Updated: Apr 5, 2026

Differentiation of Human Pluripotent Stem Cells into Insulin-Producing Islet Clusters
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Insulin-Producing Endocrine Cells Differentiated In Vitro From Human Embryonic Stem Cells Function in

Alan D Agulnick1, Dana M Ambruzs2, Mark A Moorman2

  • 1ViaCyte, Inc., San Diego, California, USA aagulnick@viacyte.com.

Stem Cells Translational Medicine
|August 26, 2015
PubMed
Summary

Human embryonic stem cell-derived pancreatic progenitors were differentiated into insulin-producing islet-like cells. These cells, when encapsulated and transplanted, matured in vivo, offering a potential cell therapy for type 1 diabetes.

Keywords:
Cell therapyDiabetesDrug delivery systemsEmbryonic stem cellsInsulin-secreting cellsPancreas development

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Area of Science:

  • Stem cell biology
  • Endocrinology
  • Regenerative medicine

Background:

  • Type 1 diabetes (T1D) is an autoimmune disease characterized by the loss of insulin-producing beta cells.
  • Current T1D management relies on exogenous insulin, which has limitations.
  • Cell replacement therapy using stem cell-derived cells is a promising alternative.

Purpose of the Study:

  • To develop an improved protocol for generating pancreatic progenitors (PPs) from human embryonic stem cells (hESCs).
  • To differentiate PPs into functional, insulin-producing islet-like cells (ICs).
  • To evaluate the in vivo function and maturation of encapsulated ICs after transplantation.

Main Methods:

  • Modified hESC differentiation protocol to enrich for PDX1+ and NKX6.1+ PPs.
  • Further differentiation of PPs into ICs with high endocrine cell content.
  • Enrichment process to remove residual PPs, yielding highly purified IC aggregates.
  • Macroencapsulation of enriched ICs and transplantation into mice.
  • Assessment of in vivo function, maturation markers, and cryopreservation capability.

Main Results:

  • Modified protocol yielded 73%-80% PDX1+/NKX6.1+ PPs.
  • Differentiated ICs comprised 73%-89% endocrine cells, with 40%-50% insulin-positive cells.
  • Enriched IC aggregates contained 93%-98% endocrine cells.
  • Encapsulated and transplanted enriched ICs demonstrated glucose-responsive insulin secretion in vivo.
  • Cryopreservation of endocrine aggregates maintained functionality.

Conclusions:

  • In vitro-produced, hESC-derived insulin-producing cells can mature and function in vivo within macroencapsulation devices.
  • Enriched ICs represent a viable cell source for T1D cell therapy.
  • Further in vivo maturation is required for optimal beta cell function.
  • The developed protocol supports scalable production and cryopreservation of functional cell aggregates.