Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells

Int J Mol Sci. 2016 Feb 19;17(2):256. doi: 10.3390/ijms17020256.

Abstract

Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.

Keywords: cell-based drug screening; diabetes mellitus; iPSC-based diabetic therapy; induced pluripotent stem cells; insulin-secreting β cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cellular Reprogramming Techniques
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / pathology
  • Drug Discovery / methods*
  • Drug Evaluation, Preclinical
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Induced Pluripotent Stem Cells / cytology*
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects
  • Models, Biological*

Substances

  • Hypoglycemic Agents