Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Stem cell-based therapy for type 1 diabetes would benefit from implementation of a cell purification step at the pancreatic endoderm stage. This would increase the safety of the final cell product, allow the establishment of an intermediate-stage stem cell bank, and provide a means for upscaling β cell manufacturing. Comparative gene expression analysis revealed glycoprotein 2 (GP2) as a specific cell surface marker for isolating pancreatic endoderm cells (PECs) from differentiated hESCs and human fetal pancreas. Isolated GP2+ PECs efficiently differentiated into glucose responsive insulin-producing cells in vitro. We found that in vitro PEC proliferation declines due to enhanced expression of the cyclin-dependent kinase (CDK) inhibitors CDKN1A and CDKN2A. However, we identified a time window when reducing CDKN1A or CDKN2A expression increased proliferation and yield of GP2+ PECs. Altogether, our results contribute tools and concepts toward the isolation and use of PECs as a source for the safe production of hPSC-derived β cells.

Detaljer

Författare
  • Jacqueline Ameri
  • Rehannah Borup
  • Christy Prawiro
  • Cyrille Ramond
  • Karen A. Schachter
  • Raphael Scharfmann
  • Henrik Semb
Enheter & grupper
Externa organisationer
  • University of Copenhagen
  • Copenhagen University Hospital
  • Paris Descartes University
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi

Nyckelord

Originalspråkengelska
Sidor (från-till)36-49
Antal sidor14
TidskriftCell Reports
Volym19
Utgivningsnummer1
StatusPublished - 2017 apr 4
PublikationskategoriForskning
Peer review utfördJa