Long-term feeder-free culture of human pancreatic progenitors on fibronectin or matrix-free polymer potentiates β cell differentiation

Akiko Nakamura, Yan Fung Wong, Andrea Venturato, Magali Michaut, Seshasailam Venkateswaran, Mithun Santra, Carla Gonçalves, Michael Larsen, Marit Leuschner, Yung Hae Kim, Joshua Brickman, Mark Bradley, Anne Grapin-Botton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

With the aim of producing β cells for replacement therapies to treat diabetes, several protocols have been developed to differentiate human pluripotent stem cells to β cells via pancreatic progenitors. While in vivo pancreatic progenitors expand throughout development, the in vitro protocols have been designed to make these cells progress as fast as possible to β cells. Here, we report on a protocol enabling a long-term expansion of human pancreatic progenitors in a defined medium on fibronectin, in the absence of feeder layers. Moreover, through a screening of a polymer library we identify a polymer that can replace fibronectin. Our experiments, comparing expanded progenitors to directly differentiated progenitors, show that the expanded progenitors differentiate more efficiently into glucose-responsive β cells and produce fewer glucagon-expressing cells. The ability to expand progenitors under defined conditions and cryopreserve them will provide flexibility in research and therapeutic production.

Original languageEnglish
Pages (from-to)1215-1228
Number of pages14
JournalStem Cell Reports
Volume17
Issue number5
Early online date21 Apr 2022
DOIs
Publication statusPublished - 10 May 2022

Keywords / Materials (for Non-textual outputs)

  • beta cells
  • differentiation
  • endocrine cells
  • human
  • long-term culture
  • pancreas
  • pancreatic progenitors
  • screening
  • transcriptome

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