A Comparison Between GalT^-/-;hCD39;hCD55 and GalT^-/-;hCD39;hCD46;hCD55;TBM Pig Kidneys Transplanted in Nonhuman Primates.

IF 3.2 4区医学 Q3 CELL & TISSUE ENGINEERING Cell Transplantation Pub Date : 2024-01-01 DOI:10.1177/09636897231217382

Han Na Suh, Ju Young Lee, Hee Jung Kang, Eun Mi Park, Ik Jin Yun, Wan Seop Kim, Kimyung Choi, Jeong Ho Hwang

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Abstract

Because there is a shortage of donor kidneys, researchers are exploring the possibility of using genetically modified pig kidneys for transplantation. Approaches involving knockout of carbohydrate genes or knockin of protective proteins have been attempted to determine the best gene modifications. In this study, we utilized GalT^-/-;hCD39;hCD55 and GalT^-/-;hCD39;hCD46;hCD55;thrombomodulin (TBM) pigs for transplantation in nonhuman primates (NHPs). The NHPs survived for 4 weeks after kidney transplantation (4 WAT) from the GalT^-/-;hCD39;hCD55 pig and for 6 WAT from the GalT^-/-;hCD39;hCD46;hCD55;TBM pig. However, messenger RNA (mRNA) sequencing and immunohistochemistry analysis revealed that the 6 WAT kidney exhibited more severe apoptosis, inflammation, loss of renal function, and renal fibrosis than the 4 WAT kidney. These results indicate that additional knockin of complement regulator (hCD46) and coagulation regulator (TBM) is not enough to prevent renal damage, suggesting that improved immune suppression is needed for more prolonged survival.

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GalT-/-;hCD39;hCD55与GalT-/-;hCD39;hCD46;hCD55;TBM猪肾移植给非人灵长类的比较。

由于供体肾脏短缺，研究人员正在探索使用转基因猪肾进行移植的可能性。为了确定最佳的基因修饰方法，研究人员尝试了敲除碳水化合物基因或敲除保护性蛋白的方法。在这项研究中，我们利用 GalT-/-;hCD39;hCD55 和 GalT-/-;hCD39;hCD46;hCD55;thrombomodulin（TBM）猪肾移植给非人灵长类动物（NHPs）。非人灵长类动物在移植 GalT-/-;hCD39;hCD55猪的肾脏（4 WAT）后存活了 4 周，在移植 GalT-/-;hCD39;hCD46;hCD55;TBM猪的肾脏（6 WAT）后存活了 6 周。然而，信使核糖核酸（mRNA）测序和免疫组化分析表明，与 4 WAT 肾脏相比，6 WAT 肾脏表现出更严重的细胞凋亡、炎症、肾功能丧失和肾脏纤维化。这些结果表明，额外敲除补体调节因子（hCD46）和凝血调节因子（TBM）不足以防止肾损伤，这表明需要改善免疫抑制以延长存活时间。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Transplantation 生物-细胞与组织工程

CiteScore

6.00

自引率

3.00%

发文量

审稿时长

6 months

期刊介绍： Cell Transplantation, The Regenerative Medicine Journal is an open access, peer reviewed journal that is published 12 times annually. Cell Transplantation is a multi-disciplinary forum for publication of articles on cell transplantation and its applications to human diseases. Articles focus on a myriad of topics including the physiological, medical, pre-clinical, tissue engineering, stem cell, and device-oriented aspects of the nervous, endocrine, cardiovascular, and endothelial systems, as well as genetically engineered cells. Cell Transplantation also reports on relevant technological advances, clinical studies, and regulatory considerations related to the implantation of cells into the body in order to provide complete coverage of the field.