Efficient vascular and neural engraftment of stem cell-derived islets. Journal Abstract

Efficient vascular and neural engraftment of stem cell-derived islets.

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Authors

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

Abstract

OBJECTIVE

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.

Source

Diabetes

Pub Types(s)

Journal Article

Language

English

PubMed ID

38603470