Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, South Korea.
J Diabetes Investig. 2024 Jun;15(6):693-703. doi: 10.1111/jdi.14216. Epub 2024 Apr 18.
AIMS/INTRODUCTION: To 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.
Donor 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.
In 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.
The 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.
目的/引言：研究各种包封异种胰岛移植的长期疗效，并探讨不同供体猪遗传特征对胰岛移植结果的影响。
从野生型、α1,3-半乳糖基转移酶敲除（GTKO）和过表达膜辅因子蛋白基因型的 GTKO 猪中获得供体猪胰岛。将裸胰岛、藻酸盐、藻酸盐-壳聚糖（AC）、藻酸盐-全氟癸烷（A-PFD）和 AC-全氟癸烷（AC-PFD）包封的猪胰岛移植到糖尿病小鼠体内。
体外评估显示，在不同的包封类型和供体猪胰岛基因型之间，胰岛的活力和功能没有差异。AC-PFD 胶囊包封的异种胰岛移植显示出最有利的长期结果，可维持正常血糖水平长达 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，裸胰岛移植后一周内血糖水平升高至>300mg/dL。根据供体胰岛基因型，裸胰岛移植结果没有改善。然而，与野生型猪胰岛相比，藻酸盐或 AC 胶囊包封的 GTKO 和过表达膜辅因子蛋白的 GTKO 猪胰岛的血糖水平升高延迟。
AC-PFD 胶囊设计用于改善缺氧和炎症，在异种胰岛移植中显示出最高的长期疗效。GTKO 或过表达膜辅因子蛋白的猪胰岛的遗传修饰对裸胰岛移植结果没有影响，但当包封时会延迟移植物衰竭。
