{"id":"doi:10.1111/dme.70507","kind":"article","title":"Characterising differential maturation of stem cell-derived islets in mice: Graft function and transcriptomic analysis","authors":["Sullivan R","Gatward LFD","Hong TW","Lyu Z","Whines WTB","Duff C","Arora R","Lonsane A","Zhao M","Salem V","King AJF","Jones PM","Persaud SJ"],"author_count":13,"year":2026,"published":"2026-10-25","venue":"Diabetic medicine : a journal of the British Diabetic Association","cited_by":0,"doi":"10.1111/dme.70507","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1111/dme.70507","archive_url":"https://space-kitty.com/papers/doi:10.1111/dme.70507","updated":null,"pmid":"42928611","pmcid":null,"openalex_id":null,"pdf_url":null,"abstract":"Aims Stem cell-derived islets (SC-islets) offer the potential to revolutionise type 1 diabetes treatment. However, functional maturation in vivo is variable, suggesting that specific, but as-yet undefined, environmental cues are critical. We aimed to identify pathways associated with SC-islet in vivo maturation in mice, assess early functional markers of this, and determine whether a hyperglycaemic graft environment impairs this. Methods Mice transplanted with 800 SC-islets but exhibiting differing glycaemic outcomes (cured, semi-cured, uncured) were selected and glucose tolerance and human C-peptide concentrations over time were measured. Single-cell transcriptomic analysis of the graft from the cured mouse was compared with in vitro-maintained SC-islets. The impact of hyperglycaemia on in vivo maturation was assessed by comparing mouse recipients of SC-islet grafts which were either hyperglycaemic or normoglycaemic for 1 month post-transplantation. Results Superior SC-islet in vivo maturation was broadly associated with progressive improvements in C-peptide and glucose tolerance. In vivo maturation was associated with a distinct transcriptomic pattern (including increased MAFA and INS expression) compared with SC-islets maintained in vitro. Finally, a hyperglycaemic post-transplant environment did not affect long-term SC-islet maturation, with no impairment in plasma human C-peptide seen at 6 months, and no changes in gene expression of β-cell maturity markers after SC-islets were transplanted into diabetic mice. Conclusion Longitudinal plasma C-peptide and glucose tolerance can be used to characterise in vivo SC-islet maturation, which is associated with transcriptomic changes not observed in vitro. Additionally, elevated blood glucose does not impair long-term functional maturation. These findings support the importance of in vivo cues for SC-islet maturation to inform future preclinical studies.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Characterising differential maturation of stem cell-derived islets in mice: Graft function and transcriptomic analysis\" by Sullivan R, Gatward LFD, Hong TW et al., https://doi.org/10.1111/dme.70507, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-cell-therapy","name":"Gene & Cell Therapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}