An arduous journey from human pluripotent stem cells to functional pancreatic β cells

Diabetes Obes Metab. 2018 Jan;20(1):3-13. doi: 10.1111/dom.12996. Epub 2017 Jun 7.

Abstract

Type 1 and type 2 diabetes are caused by a destruction and decrease in the number of functional insulin-producing β cells, respectively; therefore, the generation of functional β cells from human embryonic stem cells and human induced pluripotent stem cells, collectively known as human pluripotent stem cells (hPSCs), for potential cell replacement therapy and disease modelling is an intensely investigated area. Recent scientific breakthroughs enabled derivation of large quantities of human pancreatic β-like cells in vitro, although with varied glucose-stimulated insulin secretion kinetics. In the present review, we comprehensively summarize, compare and critically analyze the intricacies of these developing technologies, including differentiation platforms, robustness of protocols, and methodologies used to characterize hPSC-derived β-like cells. We also discuss experimental issues that need to be resolved before these β-like cells can be used clinically.

Keywords: differentiation; human; islet; pancreas; pluripotent stem cells; β cell.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Animals
  • Cell Culture Techniques / trends
  • Cell Differentiation / drug effects
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / therapy
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / therapy
  • Drug Discovery / trends
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / transplantation
  • Models, Biological*
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / drug effects
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / transplantation

Substances

  • Hypoglycemic Agents
  • Insulin