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Long‐term efficacy of encapsulated xenogeneic islet transplantation: Impact of encapsulation techniques and donor genetic traits
Journal of Diabetes Investigation ( IF 3.2 ) Pub Date : 2024-04-18 , DOI: 10.1111/jdi.14216
Heon‐Seok Park 1 , Eun Young Lee 1 , Young‐Hye You 1 , Marie Rhee 1 , Jong‐Min Kim 2 , Seong‐Soo Hwang 3 , Poong‐Yeon Lee 3
Affiliation  

Aims/IntroductionTo investigate the long‐term efficacy of various encapsulated xenogeneic islet transplantation, and to explore the impact of different donor porcine genetic traits on islet transplantation outcomes.Materials and MethodsDonor porcine islets were obtained from wild‐type, α1,3‐galactosyltransferase knockout (GTKO) and GTKO with overexpression of membrane cofactor protein genotype. Naked, alginate, alginate‐chitosan (AC), alginate‐perfluorodecalin (A‐PFD) and AC‐perfluorodecalin (AC‐PFD) encapsulated porcine islets were transplanted into diabetic mice.ResultsIn vitro assessments showed no differences in the viability and function of islets across encapsulation types and donor porcine islet genotypes. Xenogeneic encapsulated islet transplantation with AC‐PFD capsules showed the most favorable long‐term outcomes, maintaining normal blood glucose levels for 180 days. A‐PFD capsules showed comparable results to AC‐PFD capsules, followed by AC capsules and alginate capsules. Conversely, blood glucose levels in naked islet transplantation increased to >300 mg/dL within a week after transplantation. Naked islet transplantation outcomes showed no improvement based on donor islet genotype. However, alginate or AC capsules showed delayed increases in blood glucose levels for GTKO and GTKO with overexpression of membrane cofactor protein porcine islets compared with wild‐type porcine islets.ConclusionThe AC‐PFD capsule, designed to ameliorate both hypoxia and inflammation, showed the highest long‐term efficacy in xenogeneic islet transplantation. Genetic modifications of porcine islets with GTKO or GTKO with overexpression of membrane cofactor protein did not influence naked islet transplantation outcomes, but did delay graft failure when encapsulated.

中文翻译:

封装异种胰岛移植的长期疗效:封装技术和供体遗传性状的影响

目的/简介研究各种封装异种胰岛移植的长期疗效,并探讨不同供体猪遗传性状对胰岛移植结果的影响。材料与方法供体猪胰岛是从野生型、α1,3-半乳糖基转移酶敲除中获得的(GTKO) 和膜辅因子蛋白基因型过表达的 GTKO。将裸露的海藻酸盐、海藻酸盐-壳聚糖(AC)、海藻酸盐-全氟十氢萘(A-PFD)和AC-全氟十氢萘(AC-PFD)封装的猪胰岛移植到糖尿病小鼠体内。 结果体外评估显示,不同封装类型和供体猪胰岛基因型的胰岛活力和功能没有差异。采用 AC-PFD 胶囊的异种封装胰岛移植显示出最有利的长期结果,可维持正常血糖水平 180 天。 A-PFD 胶囊的结果与 AC-PFD 胶囊相当,其次是 AC 胶囊和藻酸盐胶囊。相反,裸胰岛移植中的血糖水平在移植后一周内增加至> 300 mg/dL。根据供体胰岛基因型,裸胰岛移植结果未显示改善。然而,与野生型猪胰岛相比,藻酸盐或 AC 胶囊显示 GTKO 和膜辅因子蛋白猪胰岛过表达 GTKO 的血糖水平延迟增加。结论 AC-PFD 胶囊旨在改善缺氧和炎症,表现出最高的血糖水平。异种胰岛移植的长期疗效。用GTKO或膜辅因子蛋白过表达的GTKO对猪胰岛进行基因修饰并不影响裸胰岛移植结果,但在封装时确实延迟了移植失败。
更新日期:2024-04-18
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