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Updated: Sep 28, 2026

Endothelial Cell Co-culture Mediates Maturation of Human Embryonic Stem Cell to Pancreatic Insulin Producing Cells in a Directed Differentiation Approach
08:29

Endothelial Cell Co-culture Mediates Maturation of Human Embryonic Stem Cell to Pancreatic Insulin Producing Cells in a Directed Differentiation Approach

Published on: March 27, 2012

Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells

Yuichi Hori1, Ingrid C Rulifson, Bernette C Tsai

  • 1Department of Developmental Biology and Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 21, 2002
PubMed

Insights

Embryonic stem cells treated with phosphoinositide 3-kinase inhibitors developed into insulin-producing cells. These cells effectively treated diabetes in mice, offering potential for cell-replacement therapy.

Area of Science:

  • Stem cell biology
  • Endocrinology
  • Regenerative medicine

Background:

  • Cell-replacement therapy for diabetes mellitus requires controlled differentiation of multipotent cells.
  • Embryonic stem cells (ESCs) are a potential source for therapeutic cell generation.

Purpose of the Study:

  • To investigate the potential of mouse ESCs, after specific chemical inhibition, to differentiate into functional pancreatic beta-like cells.
  • To evaluate the efficacy of these differentiated cells in treating experimental diabetes mellitus.

Main Methods:

  • Mouse ESCs were treated with inhibitors of phosphoinositide 3-kinase (PI3K).
  • Differentiated cells were characterized for beta-cell markers and insulin production.
  • Cell aggregates were transplanted into diabetic mice to assess therapeutic effects.
  • Graft survival, function, and tumor formation were analyzed.

Main Results:

  • PI3K inhibition induced ESCs to develop into cells resembling pancreatic beta cells.
  • These cells formed islet-like aggregates, produced high levels of insulin, and exhibited glucose-dependent release in vitro.
  • Transplantation of these cells in diabetic mice improved glycemic control, increased insulin levels, and rescued survival.
  • Grafted cells remained differentiated, enlarged, and did not form tumors.

Conclusions:

  • Embryonic stem cells can be differentiated into functional insulin-producing cells using PI3K inhibitors.
  • This approach shows promise for developing cell-replacement therapies for diabetes mellitus.
  • The methods may be adaptable for generating similar cells from human ESCs.

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