Stem Cell Reports (Jun 2017)

Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells

  • Jamie Trott,
  • Ee Kim Tan,
  • Sheena Ong,
  • Drew M. Titmarsh,
  • Simon L.I.J. Denil,
  • Maybelline Giam,
  • Cheng Kit Wong,
  • Jiaxu Wang,
  • Mohammad Shboul,
  • Michelle Eio,
  • Justin Cooper-White,
  • Simon M. Cool,
  • Giulia Rancati,
  • Lawrence W. Stanton,
  • Bruno Reversade,
  • N. Ray Dunn

DOI
https://doi.org/10.1016/j.stemcr.2017.05.019
Journal volume & issue
Vol. 8, no. 6
pp. 1675 – 1688

Abstract

Read online

Pluripotent stem cells have been proposed as an unlimited source of pancreatic β cells for studying and treating diabetes. However, the long, multi-step differentiation protocols used to generate functional β cells inevitably exhibit considerable variability, particularly when applied to pluripotent cells from diverse genetic backgrounds. We have developed culture conditions that support long-term self-renewal of human multipotent pancreatic progenitors, which are developmentally more proximal to the specialized cells of the adult pancreas. These cultured pancreatic progenitor (cPP) cells express key pancreatic transcription factors, including PDX1 and SOX9, and exhibit transcriptomes closely related to their in vivo counterparts. Upon exposure to differentiation cues, cPP cells give rise to pancreatic endocrine, acinar, and ductal lineages, indicating multilineage potency. Furthermore, cPP cells generate insulin+ β-like cells in vitro and in vivo, suggesting that they offer a convenient alternative to pluripotent cells as a source of adult cell types for modeling pancreatic development and diabetes.

Keywords