Induced pluripotent stem cells as a model for diabetes investigation

Sci Rep. 2015 Feb 26:5:8597. doi: 10.1038/srep08597.

Abstract

Mouse and human induced pluripotent stem cells (iPSCs) may represent a novel approach for modeling diabetes. Taking this into consideration, the aim of this study was to generate and evaluate differentiation potential of iPSCs from lep(db/db) (db/db) mice, the model of diabetes type 2 as well as from patients with Maturity Onset Diabetes of the Young 3 (HNF1A MODY). Murine iPSC colonies from both wild type and db/db mice were positive for markers of pluripotency: Oct3/4A, Nanog, SSEA1, CDy1 and alkaline phosphatase and differentiated in vitro and in vivo into cells originating from three germ layers. However, our results suggest impaired differentiation of db/db cells into endothelial progenitor-like cells expressing CD34 and Tie2 markers and their reduced angiogenic potential. Human control and HNF1A MODY reprogrammed cells also expressed pluripotency markers: OCT3/4A, SSEA4, TRA-1-60, TRA-1-81, formed embryoid bodies (EBs) and differentiated into cells of three germ layers. Additionally, insulin expressing cells were obtained from those partially reprogrammed cells with direct as well as EB-mediated differentiation method. Our findings indicate that disease-specific iPSCs may help to better understand the mechanisms responsible for defective insulin production or vascular dysfunction upon differentiation toward cell types affected by diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Biomarkers
  • Cell Differentiation
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / pathology*
  • Embryoid Bodies / metabolism
  • Endothelial Progenitor Cells / metabolism
  • Female
  • Homeodomain Proteins / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Lewis X Antigen / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Obese
  • Middle Aged
  • Nanog Homeobox Protein
  • Nuclear Proteins / metabolism
  • Octamer Transcription Factor-3 / metabolism

Substances

  • Biomarkers
  • Homeodomain Proteins
  • Lewis X Antigen
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Nuclear Proteins
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse