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Ameri, J.* ; Borup, R.* ; Prawiro, C.* ; Ramond, C.* ; Schachter, K.A.* ; Scharfmann, R.* ; Semb, H.

Efficient generation of glucose-responsive beta cells from isolated GP2+ human pancreatic progenitors.

Cell Rep. 19, 36-49 (2017)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cdkn1a ; Cdkn2a ; Gp2 ; Cell Surface Marker ; Cell-cycle Regulators ; Differentiation ; Human Embryonic Stem Cells ; Insulin-producing Beta Cells ; Pancreatic Progenitors ; Type 1 Diabetes
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 19, Heft: 1, Seiten: 36-49 Artikelnummer: , Supplement: ,
Verlag Cell Press
Begutachtungsstatus Peer reviewed