Long-term feeder-free culture of human pancreatic progenitors on fibronectin or matrix-free polymer potentiates β cell differentiation
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Long-term feeder-free culture of human pancreatic progenitors on fibronectin or matrix-free polymer potentiates β cell differentiation. / Nakamura, Akiko; Wong, Yan Fung; Venturato, Andrea; Michaut, Magali; Venkateswaran, Seshasailam; Santra, Mithun; Gonçalves, Carla; Larsen, Michael; Leuschner, Marit; Kim, Yung Hae; Brickman, Joshua; Bradley, Mark; Grapin-Botton, Anne.
I: Stem Cell Reports, Bind 17, Nr. 5, 2022, s. 1215-1228.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Long-term feeder-free culture of human pancreatic progenitors on fibronectin or matrix-free polymer potentiates β cell differentiation
AU - Nakamura, Akiko
AU - Wong, Yan Fung
AU - Venturato, Andrea
AU - Michaut, Magali
AU - Venkateswaran, Seshasailam
AU - Santra, Mithun
AU - Gonçalves, Carla
AU - Larsen, Michael
AU - Leuschner, Marit
AU - Kim, Yung Hae
AU - Brickman, Joshua
AU - Bradley, Mark
AU - Grapin-Botton, Anne
N1 - Publisher Copyright: © 2022 The Authors
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - beta cells
KW - differentiation
KW - endocrine cells
KW - human
KW - long-term culture
KW - pancreas
KW - pancreatic progenitors
KW - screening
KW - transcriptome
U2 - 10.1016/j.stemcr.2022.03.013
DO - 10.1016/j.stemcr.2022.03.013
M3 - Journal article
C2 - 35452596
AN - SCOPUS:85129598401
VL - 17
SP - 1215
EP - 1228
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 5
ER -
ID: 307330469