Targeted Derivation of Organotypic Glucose- and GLP-1-Responsive β Cells Prior to Transplantation into Diabetic Recipients
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved..
Generation of functional β cells from pluripotent sources would accelerate diagnostic and therapeutic applications for diabetes research and therapy. However, it has been challenging to generate competent β cells with dynamic insulin-secretory capacity to glucose and incretin stimulations. We introduced transcription factors, critical for β-cell development and function, in differentiating human induced pluripotent stem cells (PSCs) and assessed the impact on the functionality of derived β-cell (psBC) progeny. A perifusion system revealed stepwise transduction of the PDX1, NEUROG3, and MAFA triad (PNM) enabled in vitro generation of psBCs with glucose and GLP-1 responsiveness within 3 weeks. PNM transduction upregulated genes associated with glucose sensing, insulin secretion, and β-cell maturation. In recipient diabetic mice, PNM-transduced psBCs showed glucose-responsive insulin secretion as early as 1 week post transplantation. Thus, enhanced pre-emptive β-cell specification of PSCs by PNM drives generation of glucose- and incretin-responsive psBCs in vitro, offering a competent tissue-primed biotherapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Stem cell reports - 13(2019), 2 vom: 13. Aug., Seite 307-321 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhu, Yaxi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.04.2020 Date Revised 20.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.stemcr.2019.07.006 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Generation of functional β cells from pluripotent sources would accelerate diagnostic and therapeutic applications for diabetes research and therapy. However, it has been challenging to generate competent β cells with dynamic insulin-secretory capacity to glucose and incretin stimulations. We introduced transcription factors, critical for β-cell development and function, in differentiating human induced pluripotent stem cells (PSCs) and assessed the impact on the functionality of derived β-cell (psBC) progeny. A perifusion system revealed stepwise transduction of the PDX1, NEUROG3, and MAFA triad (PNM) enabled in vitro generation of psBCs with glucose and GLP-1 responsiveness within 3 weeks. PNM transduction upregulated genes associated with glucose sensing, insulin secretion, and β-cell maturation. In recipient diabetic mice, PNM-transduced psBCs showed glucose-responsive insulin secretion as early as 1 week post transplantation. Thus, enhanced pre-emptive β-cell specification of PSCs by PNM drives generation of glucose- and incretin-responsive psBCs in vitro, offering a competent tissue-primed biotherapy | ||
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| 700 | 1 | |a Schreiber, Claire A |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Zhiguang |e verfasserin |4 aut | |
| 700 | 1 | |a Rakshit, Kuntol |e verfasserin |4 aut | |
| 700 | 1 | |a Matveyenko, Aleksey V |e verfasserin |4 aut | |
| 700 | 1 | |a Terzic, Andre |e verfasserin |4 aut | |
| 700 | 1 | |a Wigle, Dennis |e verfasserin |4 aut | |
| 700 | 1 | |a Kudva, Yogish C |e verfasserin |4 aut | |
| 700 | 1 | |a Ikeda, Yasuhiro |e verfasserin |4 aut | |
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