GP2-enriched pancreatic progenitors give rise to functional beta cells in vivo and eliminate the risk of teratoma formation.

Autor:	Aghazadeh Y; McEwen Stem Cell Institute, University Health Network, 101 College Street MaRS, PMCRT 3-916, Toronto, ON M5G 1L7, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada., Sarangi F; McEwen Stem Cell Institute, University Health Network, 101 College Street MaRS, PMCRT 3-916, Toronto, ON M5G 1L7, Canada., Poon F; McEwen Stem Cell Institute, University Health Network, 101 College Street MaRS, PMCRT 3-916, Toronto, ON M5G 1L7, Canada; Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Nkennor B; Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Biological Sciences, University of Toronto, Scarborough, ON M1C 1A4, Canada., McGaugh EC; McEwen Stem Cell Institute, University Health Network, 101 College Street MaRS, PMCRT 3-916, Toronto, ON M5G 1L7, Canada; Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Nunes SS; Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Heart & Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON M5S 3H2, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Nostro MC; McEwen Stem Cell Institute, University Health Network, 101 College Street MaRS, PMCRT 3-916, Toronto, ON M5G 1L7, Canada; Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: cnostro@uhnresearch.ca.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2022 Apr 12; Vol. 17 (4), pp. 964-978. Date of Electronic Publication: 2022 Mar 31.
DOI:	10.1016/j.stemcr.2022.03.004
Abstrakt:	Human pluripotent stem cell (hPSC)-derived pancreatic progenitors (PPs) can be differentiated into beta-like cells in vitro and in vivo and therefore have therapeutic potential for type 1 diabetes (T1D) treatment. However, the purity of PPs varies across different hPSC lines, differentiation protocols, and laboratories. The uncommitted cells may give rise to non-pancreatic endodermal, mesodermal, or ectodermal derivatives in vivo, hampering the safety of hPSC-derived PPs for clinical applications and their differentiation efficiency in research settings. Recently, proteomics and transcriptomics analyses identified glycoprotein 2 (GP2) as a PP-specific cell surface marker. The GP2-enriched PPs generate higher percentages of beta-like cells in vitro, but their potential in vivo remains to be elucidated. Here, we demonstrate that the GP2-enriched-PPs give rise to all pancreatic cells in vivo, including functional beta-like cells. Remarkably, GP2 enrichment eliminates the risk of teratomas, which establishes GP2 sorting as an effective method for PP purification and safe pancreatic differentiation. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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