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基因编辑、基因治疗与细胞异种移植:跨物种的细胞移植

Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species.

作者信息

Mourad Nizar I, Gianello Pierre

机构信息

Pôle de chirurgie expérimentale et transplantation, Université catholique de Louvain, SSS/IREC/CHEX, Avenue Hippocrate, 55 - Bte B1.55.04, 1200 Brussels, Belgium.

出版信息

Curr Transplant Rep. 2017;4(3):193-200. doi: 10.1007/s40472-017-0157-6. Epub 2017 Jul 21.

DOI:10.1007/s40472-017-0157-6
PMID:28932650
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5577055/
Abstract

PURPOSE OF REVIEW

Cell xenotransplantation has the potential to provide a safe, ethically acceptable, unlimited source for cell replacement therapies. This review focuses on genetic modification strategies aimed to overcome remaining hurdles standing in the way of clinical porcine islet transplantation and to develop neural cell xenotransplantation.

RECENT FINDINGS

In addition to previously described genetic modifications aimed to mitigate hyperacute rejection, instant blood-mediated inflammatory reaction, and cell-mediated rejection, new data showing the possibility of increasing porcine islet insulin secretion by transgenesis is an interesting addition to the array of genetically modified pigs available for xenotransplantation. Moreover, combining multiple modifications is possible today thanks to new, improved genomic editing tools.

SUMMARY

Genetic modification of large animals, pigs in particular, has come a long way during the last decade. These modifications can help minimize immunological and physiological incompatibilities between porcine and human cells, thus allowing for better tolerance and function of xenocells.

摘要

综述目的

细胞异种移植有潜力为细胞替代疗法提供一个安全、符合伦理且来源不受限的途径。本综述聚焦于旨在克服临床猪胰岛移植所面临的现存障碍以及发展神经细胞异种移植的基因改造策略。

最新发现

除了先前描述的旨在减轻超急性排斥反应、即时血液介导的炎症反应和细胞介导的排斥反应的基因改造外,新数据表明通过转基因增加猪胰岛胰岛素分泌的可能性,这为可用于异种移植的转基因猪增添了一个有趣的补充。此外,由于新的、改进的基因组编辑工具,如今可以将多种改造结合起来。

总结

在过去十年中,大型动物尤其是猪的基因改造取得了长足进展。这些改造有助于最大限度地减少猪和人类细胞之间的免疫和生理不相容性,从而使异种细胞具有更好的耐受性和功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe7/5577055/13ee6f738eac/40472_2017_157_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe7/5577055/06d9db967917/40472_2017_157_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe7/5577055/13ee6f738eac/40472_2017_157_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe7/5577055/06d9db967917/40472_2017_157_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe7/5577055/13ee6f738eac/40472_2017_157_Fig2_HTML.jpg

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Porcine Islet Xenografts: a Clinical Source of ß-Cell Grafts.猪胰岛异种移植:β细胞移植的临床来源
Curr Diab Rep. 2017 Mar;17(3):14. doi: 10.1007/s11892-017-0846-7.
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Transgenic expression of human leukocyte antigen-E attenuates GalKO.hCD46 porcine lung xenograft injury.人白细胞抗原-E的转基因表达减轻了GalKO.hCD46猪肺异种移植损伤。
胰岛移植在生物制品许可申请(BLA)获批后的未来:挑战与机遇
Front Transplant. 2025 Mar 7;4:1522409. doi: 10.3389/frtra.2025.1522409. eCollection 2025.
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Enhanced Insulin Production From Porcine Islets: More Insulin, Less Islets.猪胰岛胰岛素分泌增强:胰岛素增多,胰岛减少。
Transpl Int. 2024 Dec 18;37:13954. doi: 10.3389/ti.2024.13954. eCollection 2024.
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