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Efficient Generatio...
Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors
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- Ameri, Jacqueline (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,University of Copenhagen
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- Borup, Rehannah (author)
- Copenhagen University Hospital
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- Prawiro, Christy (author)
- University of Copenhagen
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- Ramond, Cyrille (author)
- Paris Descartes University
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- Schachter, Karen A. (author)
- University of Copenhagen
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- Scharfmann, Raphael (author)
- Paris Descartes University
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- Semb, Henrik (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,University of Copenhagen
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(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English 14 s.
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 19:1, s. 36-49
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http://dx.doi.org/10... (free)
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Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- CDKN1A
- CDKN2A
- cell surface marker
- cell-cycle regulators
- differentiation
- GP2
- human embryonic stem cells
- insulin-producing beta cells
- pancreatic progenitors
- type 1 diabetes
Publication and Content Type
- art (subject category)
- ref (subject category)
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