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.

中文翻译：

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干细胞来源的胰岛的有效血管和神经移植

多能干细胞衍生的胰岛 (SC-islet) 现在成为 β 细胞替代疗法的新来源。虽然人类胰岛移植的功能受到移植后过度细胞死亡的阻碍，影响因素包括炎症反应、血运重建不足和胰岛淀粉样蛋白形成，但对 SC 胰岛的植入过程的了解仍存在空白。在本实验研究中，我们研究了SC-胰岛在移植后三个月的植入能力，并观察到细胞凋亡率较低，但SC-胰岛的血管密度与人类胰岛相似。虽然人胰岛移植血管结构是残余供体内皮和内生长血管的混合物，但 SC 胰岛仅包含内生长血管。 SC 胰岛移植物的氧合作用是相应的人类胰岛移植物的两倍，表明血管功能更好。与血管向内生长类似，SC 胰岛的神经支配也比人类胰岛高四到五倍。 SC 胰岛和人类胰岛在移植后 1 个月和 3 个月都含有淀粉样蛋白。我们得出的结论是，SC 胰岛的血管和神经移植优于人类胰岛，但两种来源的移植物都会产生淀粉样蛋白，具有潜在的长期后果。