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bioRxiv · 10.1101/2021.05.15.444293

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

Aghazadeh, Y.·Sarangi, F.·Poon, F.·Nkennor, B.·McGaugh, E.·Nunes, S. S.·Nostro, M. C.
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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. 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 compared to unsorted and GP2- fractions, 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 eliminated the formation of teratoma in vivo. This study establishes that the GP2-enriched PPs represent a safe option for T1D treatment.

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Aghazadeh, Y., Sarangi, F., Poon, F., Nkennor, B., McGaugh, E., Nunes, S. S., Nostro, M. C.. 2021-05-16. GP2-enriched pancreatic progenitors give rise to functional beta cells in vivo and eliminate the risk of teratoma formation. https://doi.org/10.1101/2021.05.15.444293

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