GP2-enriched pancreatic progenitors give rise to functional beta cells in vivo and eliminate the risk of teratoma formation
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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.
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Ensuring the pancreatic progenitor population expressed the glycoprotein GP2 prevented tumor formation upon transplantation.
“Interestingly, it was demonstrated that ensuring the pancreatic progenitor population expressed the glycoprotein GP2 prevented tumor formation upon transplantation, suggesting that dangerous cell populations in the final cell product can potentially be identified earlier in the differentiation.161”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [161]
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The comparative cell physiology of stem cell-derived and primary human β cells
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- Authors
- Aghazadeh, Y., Sarangi, F., Poon, F., Nkennor, B., McGaugh, E. C., Nunes, S. S., & Nostro, M. C.
- Affiliations
- University Health Network (CA)
- Corresponding author
- Nostro, M. Cristina
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2022-04
- Volume
- 17
- Issue
- 4
- Pages
- 964-978
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC9023812
- OpenAlex
- W4225679609
- Cited by
- 62
- References
- 63
- Citations by year
- 2026: 6 · 2025: 19 · 2024: 19 · 2023: 13 · 2022: 5
- FWCI
- 13.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Toronto General Hospital Research Institute, University Health Network
- Banting and Best Diabetes Centre, University of Toronto
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- GP2, pancreatic progenitors, beta cell differentiation, teratoma formation, human pluripotent stem cells, pancreatic differentiation, type 1 diabetes, cell purification, in vivo differentiation
- MeSH terms
- Cell Differentiation, Endoderm, Humans, Pancreas, Teratoma, Pluripotent Stem Cells, Insulin-Secreting Cells
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