Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors
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Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors. / Ameri, Jacqueline; Borup, Rehannah ; Prawiro, Christy; Ramond, Cyrille; Schachter, Karen; Scharfmann, Raphael ; Semb, Tor Henrik.
In: Cell Reports, Vol. 19, No. 1, 04.04.2017, p. 36-49.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors
AU - Ameri, Jacqueline
AU - Borup, Rehannah
AU - Prawiro, Christy
AU - Ramond, Cyrille
AU - Schachter, Karen
AU - Scharfmann, Raphael
AU - Semb, Tor Henrik
PY - 2017/4/4
Y1 - 2017/4/4
N2 - 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.
AB - 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.
U2 - 10.1016/j.celrep.2017.03.032
DO - 10.1016/j.celrep.2017.03.032
M3 - Journal article
C2 - 28380361
VL - 19
SP - 36
EP - 49
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 1
ER -
ID: 174896633