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Endocrine-enriched stem cell-derived islets improve long-term safety in vivo

Setyono, E. S. A.; Rogers, N. K.; Scheibner, K.; Schirge, S.; Reich, H.; Sterr, M.; Öztürk, T.; Franzenburg, S.; Lithovius, V.; Lickert, H.

2025-08-23 bioengineering
10.1101/2025.08.22.671768 bioRxiv
Show abstract

Fully differentiated stem cell-derived islets (SC-islets) are proven to normalise blood glucose in type 1 diabetic patients. However, the presence of off-target cell types and the immature SC-islet function upon transplantation remain unresolved problems. Here, we established sorting strategies to generate SC-islets with defined glucagon-producing SC-- and insulin-producing {beta}-cell ratios and assessed their safety and efficacy in vitro and in vivo. Engineering SC-islets is beneficial to the insulin response in vitro, which does not translate to improved glycaemic regulation in vivo. Importantly, hormone-producing endocrine cell enrichment and thus off-target cell type depletion eliminated the risk for unwanted outgrowth in vivo. Single cell analysis defined off-target cells in vitro and in vivo and identified marker genes to assess SC-islet quality and define safety release criteria before graft transplantation. This study highlights the importance of determining the SC-islet composition and establishing rigorous quality controls to ensure long-term safety for {beta}-cell replacement therapy.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.