Alginate encapsulation as long |
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Alginate encapsulation as long
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The transplantation of pancreatic islet cells could restore glycaemic control in patients with type-I diabetes. Microspheres for islet encapsulation have enabled long-term glycaemic control in diabetic rodent models; yet human patients transplanted with equivalent microsphere formulations have experienced only transient islet-graft function, owing to a vigorous foreign-body reaction (FBR), to pericapsular fibrotic overgrowth (PFO) and, in upright bipedal species, to the sedimentation of the microspheres within the peritoneal cavity. Here, we report the results of the testing, in non-human primate (NHP) models, of seven alginate formulations that were efficacious in rodents, including three that led to transient islet-graft function in clinical trials. Although one month post-implantation all formulations elicited significant FBR and PFO, three chemically modified, immune-modulating alginate formulations elicited reduced FBR. In conjunction with a minimally invasive transplantation technique into the bursa omentalis of NHPs, the most promising chemically modified alginate derivative (Z1-Y15) protected viable and glucose-responsive allogeneic islets for 4 months without the need for immunosuppression. Chemically modified alginate formulations may enable the long-term transplantation of islets for the correction of insulin deficiency.
中文翻译：
胰岛细胞移植可以恢复 I 型糖尿病患者的血糖控制。用于胰岛封装的微球能够在糖尿病啮齿动物模型中实现长期血糖控制；然而，由于强烈的异物反应（FBR）、囊周纤维化过度生长（PFO）以及直立双足物种中的微球沉积，移植了同等微球制剂的人类患者仅经历了短暂的胰岛移植功能。腹膜腔。在这里，我们报告了在非人类灵长类动物 (NHP) 模型中对啮齿动物有效的七种藻酸盐制剂的测试结果，其中三种在临床试验中导致短暂的胰岛移植功能。尽管植入后 1 个月，所有制剂均引起显着的 FBR 和 PFO，但三种化学修饰的免疫调节藻酸盐制剂引起 FBR 降低。与 NHP 网膜囊的微创移植技术相结合，最有前途的化学修饰藻酸盐衍生物 (Z1-Y15) 可以保护存活且具有葡萄糖反应性的同种异体胰岛 4 个月，而无需免疫抑制。化学修饰的藻酸盐制剂可以实现胰岛的长期移植以纠正胰岛素缺乏。 |
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