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

Yasaman Aghazadeh; Farida Sarangi; Frankie Poon; Blessing Nkennor; Emily C McGaugh; Sara S Nunes; M Cristina Nostro

doi:10.1016/j.stemcr.2022.03.004

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

Stem Cell Reports. 2022 Apr 12;17(4):964-978. doi: 10.1016/j.stemcr.2022.03.004. Epub 2022 Mar 31.

Authors

Yasaman Aghazadeh¹, Farida Sarangi², Frankie Poon³, Blessing Nkennor⁴, Emily C McGaugh³, Sara S Nunes⁵, M Cristina Nostro⁶

Affiliations

¹ 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.
² McEwen Stem Cell Institute, University Health Network, 101 College Street MaRS, PMCRT 3-916, Toronto, ON M5G 1L7, Canada.
³ 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.
⁴ 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.
⁵ 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.
⁶ 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.

Abstract

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.

Keywords: beta cells; cell replacement therapy; cell surface marker; ectoderm; endoderm; human embryonic stem cells; mesoderm; pancreatic progenitors; teratoma; type 1 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation / physiology
Endoderm
Humans
Insulin-Secreting Cells* / metabolism
Pancreas
Pluripotent Stem Cells* / metabolism
Teratoma* / etiology
Teratoma* / metabolism

Grants and funding

CIHR/Canada