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Efficient vascular and neural engraftment of stem cell-derived islets

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posted on 2024-04-11, 17:56 authored by Julia Thorngren, Anja Brboric, Svitlana Vasylovska, Daisy Hjelmqvist, Gunilla T Westermark, Jonna Saarimäki-Vire, Jouni Kvist, Diego Balboa, Timo Otonkoski, Per-Ola Carlsson, Joey Lau

Pluripotent stem cell-derived islets (SC-islets) now emerge as a new source for beta-cell replacement therapy. While the function of human islet transplants is hampered by excessive cell death post-transplantation, contributing factors include inflammatory reactions, insufficient revascularization and islet amyloid formation, there is a gap in knowledge on the engraftment process of the SC-islets. In this experimental study, we investigated the engraftment capability of SC-islets at three months post-transplantation, and observed that the cell apoptosis rates were lower, but the vascular density was similar in SC-islets to that of human islets. While the human islet transplant vascular structures were a mixture of remnant donor endothelium and ingrowing blood vessels, the SC-islets contained ingrowing blood vessels only. The oxygenation of the SC-islet grafts was twice as high as in the corresponding grafts of human islets, suggesting better vascular functionality. Similar to the blood vessel ingrowth, also the reinnervation of the SC-islets was four- to five-fold higher than the human islets. Both SC-islets and the human islets contained amyloid at one and three months post-transplantation. We conclude that the vascular and neural engraftment of SC-islets is superior to human islets, but that grafts of both origins develop amyloid with potential long-term consequences.

Funding

This work was supported by the Swedish Research Council (55X-15043, 2017-01343), the Swedish Child Diabetes Fund, the Swedish Diabetes Foundation, Diabetes Wellness Sverige, the Novo Nordisk Foundation, the family Erling Persson foundation, the Ernfors family foundation, as well as the national strategic research programmes Excellence of Diabetes Research in Sweden (Exodiab) and StemTherapy. The work in Helsinki was supported by The Academy of Finland Center of Excellence Metastem (312437), the Sigrid Jusélius Foundation, the Novo Nordisk Foundation and the Wellcome Collaborative Award (224600/Z/21/Z).

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