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Updated: Sep 23, 2025

Differentiation of Human Pluripotent Stem Cells into Insulin-Producing Islet Clusters
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Adapting Physiology in Functional Human Islet Organogenesis.

Eiji Yoshihara1,2

  • 1Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States.

Frontiers in Cell and Developmental Biology
|May 13, 2022
PubMed
Summary

Generating functional human islets from pluripotent stem cells offers a promising alternative for diabetes treatment. Further research is needed to achieve full maturity and functionality comparable to primary human islets for transplantation.

Keywords:
diabeteshuman islet-like organoidshuman pluripotent stem cellsnuclear receptorsphysiology

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Area of Science:

  • Stem cell biology
  • Endocrinology
  • Regenerative medicine

Background:

  • Human pluripotent stem cells (hPSCs) provide an abundant source for generating human islets.
  • Current hPSC-derived islets are functionally immature compared to primary human islets.
  • Challenges remain in creating fully functional, transplantable human islets in vitro.

Purpose of the Study:

  • To review progress in generating 3D-structured human islets from pluripotent stem cells.
  • To discuss the importance of physiological adaptation for in vitro human islet organogenesis.
  • To explore potential improvements using environmental cues for islet maturation.

Main Methods:

  • Review of current literature on hPSC differentiation into islet-like clusters.
  • Analysis of factors influencing islet maturation and functionality.
  • Discussion of strategies for in vitro organogenesis.

Main Results:

  • hPSC technology enables differentiation into glucose-sensing, insulin-secreting islet-like clusters.
  • Transplantation of these clusters can ameliorate diabetes in preclinical models (rodents, NHPs).
  • Significant functional and transcriptional immaturity persists in hPSC-derived islets.

Conclusions:

  • Achieving fully functional human islets in vitro requires understanding complex differentiation pathways.
  • Adapting physiological conditions and incorporating environmental cues are crucial for in vitro organogenesis.
  • Further advancements are necessary to generate a consistent supply of high-quality human islets for diabetes treatment.