Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors
(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
- Ameri, Jacqueline LU ; Borup, Rehannah ; Prawiro, Christy ; Ramond, Cyrille ; Schachter, Karen A. LU ; Scharfmann, Raphael and Semb, Henrik LU
- organization
- publishing date
- 2017-04-04
- 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
- 2024-03-31 08:28:39
@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}},
}