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- Title
Efficient Vascular and Neural Engraftment of Stem Cell–Derived Islets.
- Authors
Thorngren, Julia; Brboric, Anja; Vasylovska, Svitlana; Hjelmqvist, Daisy; Westermark, Gunilla T.; Saarimäki-Vire, Jonna; Kvist, Jouni; Balboa, Diego; Otonkoski, Timo; Carlsson, Per-Ola; Lau, Joey
- Abstract
Pluripotent stem cell–derived islets (SC-islets) have emerged as a new source for β-cell replacement therapy. The function of human islet transplants is hampered by excessive cell death posttransplantation; contributing factors include inflammatory reactions, insufficient revascularization, and islet amyloid formation. However, there is a gap in knowledge of the engraftment process of SC-islets. In this experimental study, we investigated the engraftment capability of SC-islets at 3 months posttransplantation and observed that cell apoptosis rates were lower but vascular density was similar in SC-islets compared with human islets. Whereas 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. Oxygenation in the SC-islet grafts was twice as high as that in the corresponding grafts of human islets, suggesting better vascular functionality. Similar to the blood vessel ingrowth, reinnervation of the SC-islets was four- to fivefold higher than that of the human islets. Both SC-islets and human islets contained amyloid at 1 and 3 months posttransplantation. We conclude that the vascular and neural engraftment of SC-islets are superior to those of human islets, but grafts of both origins develop amyloid, with potential long-term consequences. Article Highlights: There is a gap in knowledge of the engraftment process of stem cell–derived islets (SC-islets). We investigated the engraftment capability of SC-islets compared with that of human islets after transplantation. Vascular density was similar in SC-islets and human islets, but neural density was four- to fivefold higher in SC-islets than in human islets. Vascular and neural engraftment of SC-islets are superior to those of human islets.
- Subjects
ISLANDS; VASCULAR endothelium; BLOOD vessels
- Publication
Diabetes, 2024, Vol 73, Issue 7, p1127
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db23-0123