Hypoxia is a major cause of considerable islet loss during the early post-transplantation period. Here, we investigate whether shielding islets with human amniotic epithelial cells (hAECs), which possess anti-inflammatory and regenerative properties, improves islet engraftment and survival. Shielded islets were generated on agarose microwells by mixing rat (RI) or human (HI) islets and hAECs (100 hAECs/IEQ). Islet secretory function and viability were assessed after culture in hypoxia (1% O2) or normoxia (21% O2) in vitro. In vivo function was evaluated after transplantation under the kidney capsule of diabetic immunodeficient mice. Graft morphology and vascularization were evaluated by immunohistochemistry. Both shielded RI and HI show higher viability and increased glucose-stimulated insulin secretion after exposure to hypoxia in vitro compared to control islets. Transplantation of shielded islets results in considerably earlier normoglycemia and vascularization, an enhanced glucose tolerance and a higher β-cell mass. Our results how that hAECs have a clear cytoprotective effect against hypoxic damages in vitro. This strategy improves β-cell mass engraftment and islet revascularization, leading to an improved capacity of islets to reverse hyperglycaemia, and could be rapidly applicable in the clinical situation seeing that the modification to human islets are minor.

中文翻译：

---

用人羊膜上皮细胞保护胰岛可增强小鼠糖尿病模型中的胰岛植入和血运重建。

缺氧是移植后早期大量胰岛丢失的主要原因。在这里，我们研究了用具有抗炎和再生特性的人羊膜上皮细胞 (hAEC) 屏蔽胰岛是否可以改善胰岛植入和存活。通过混合大鼠 (RI) 或人类 (HI) 胰岛和 hAEC (100 hAEC/IEQ)，在琼脂糖微孔上生成屏蔽胰岛。在缺氧 (1% O2) 或常氧 (21% O2) 体外培养后评估胰岛分泌功能和活力。在糖尿病免疫缺陷小鼠的肾囊下移植后评估体内功能。通过免疫组织化学评估移植物形态和血管形成。与对照胰岛相比，在体外暴露于低氧环境后，屏蔽的 RI 和 HI 均显示出更高的活力和增加的葡萄糖刺激的胰岛素分泌。屏蔽胰岛移植可显着提早出现血糖正常和血管形成、葡萄糖耐量增强和 β 细胞量增加。我们的结果表明 hAEC 如何在体外对缺氧损伤具有明显的细胞保护作用。该策略改善了 β 细胞大量植入和胰岛血运重建，从而提高了胰岛逆转高血糖的能力，并且由于对人类胰岛的修饰很小，因此可以快速应用于临床情况。我们的结果表明 hAEC 如何在体外对缺氧损伤具有明显的细胞保护作用。该策略改善了 β 细胞大量植入和胰岛血运重建，从而提高了胰岛逆转高血糖的能力，并且由于对人类胰岛的修饰很小，因此可以快速应用于临床情况。我们的结果表明 hAEC 如何在体外对缺氧损伤具有明显的细胞保护作用。该策略改善了 β 细胞大量植入和胰岛血运重建，从而提高了胰岛逆转高血糖的能力，并且由于对人类胰岛的修饰很小，因此可以快速应用于临床情况。