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

Ameri, Jacqueline LU ; Borup, Rehannah ; Prawiro, Christy ; Ramond, Cyrille ; Schachter, Karen A. LU ; Scharfmann, Raphael and Semb, Henrik LU (2017) In Cell Reports 19(1). p.36-49
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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CDKN1A, CDKN2A, cell surface marker, cell-cycle regulators, differentiation, GP2, human embryonic stem cells, insulin-producing beta cells, pancreatic progenitors, type 1 diabetes
in
Cell Reports
volume
19
issue
1
pages
14 pages
publisher
Cell Press
external identifiers
  • scopus:85016930711
  • pmid:28380361
  • wos:000398231800004
ISSN
2211-1247
DOI
10.1016/j.celrep.2017.03.032
language
English
LU publication?
yes
id
12ac3ce7-c77e-4d6e-aa1f-867826379b86
date added to LUP
2017-04-27 14:19:24
date last changed
2022-05-10 07:37:27
@article{12ac3ce7-c77e-4d6e-aa1f-867826379b86,
  abstract     = {{<p>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<sup>+</sup> 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<sup>+</sup> 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.</p>}},
  author       = {{Ameri, Jacqueline and Borup, Rehannah and Prawiro, Christy and Ramond, Cyrille and Schachter, Karen A. and Scharfmann, Raphael and Semb, Henrik}},
  issn         = {{2211-1247}},
  keywords     = {{CDKN1A; CDKN2A; cell surface marker; cell-cycle regulators; differentiation; GP2; human embryonic stem cells; insulin-producing beta cells; pancreatic progenitors; type 1 diabetes}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{1}},
  pages        = {{36--49}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2<sup>+</sup> Human Pancreatic Progenitors}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2017.03.032}},
  doi          = {{10.1016/j.celrep.2017.03.032}},
  volume       = {{19}},
  year         = {{2017}},
}