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肝移植的未来:诱导多能干细胞的非人类灵长类动物患者特异性器官。

Future of liver transplantation: non-human primates for patient-specific organs from induced pluripotent stem cells.

机构信息

Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110070, India.

出版信息

World J Gastroenterol. 2011 Aug 28;17(32):3684-90. doi: 10.3748/wjg.v17.i32.3684.

Abstract

Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the complex relations between different cell types, generation of adequate vasculature, and immunological complications are road blocks in generation of bioengineered organs, while immunological complications limit the use of humanized organs produced in animals. Recent developments in induced pluripotent stem cell (iPSC) biology offer a possibility of generating human, patient-specific organs in non-human primates (NHP) using patient-derived iPSC and NHP-derived iPSC lacking the critical developmental genes for the organ of interest complementing a NHP tetraploid embryo. The organ derived in this way will have the same human leukocyte antigen (HLA) profile as the patient. This approach can be curative in genetic disorders as this offers the possibility of gene manipulation and correction of the patient's genome at the iPSC stage before tetraploid complementation. The process of generation of patient-specific organs such as the liver in this way has the great advantage of making use of the natural signaling cascades in the natural milieu probably resulting in organs of great quality for transplantation. However, the inexorable scientific developments in this direction involve several social issues and hence we need to educate and prepare society in advance to accept the revolutionary consequences, good, bad and ugly.

摘要

填补人体器官供需巨大缺口的策略包括生物人工器官、在动物体内培育人源化器官、细胞疗法和可植入的生物工程构建体。在生成生物工程器官过程中,不同细胞类型之间的复杂关系、足够的脉管系统生成以及免疫并发症是障碍,而免疫并发症限制了在动物体内产生的人源化器官的使用。诱导多能干细胞 (iPSC) 生物学的最新进展为使用患者来源的 iPSC 和缺乏感兴趣器官关键发育基因的非人灵长类动物 (NHP) 来源的 iPSC 在非人类灵长类动物 (NHP) 中生成人类、患者特异性器官提供了可能性,补充 NHP 四倍体胚胎。以这种方式衍生的器官将具有与患者相同的人类白细胞抗原 (HLA) 谱。这种方法在遗传性疾病中具有治疗作用,因为它提供了在四倍体互补之前在 iPSC 阶段对患者基因组进行基因操作和纠正的可能性。以这种方式生成患者特异性器官(如肝脏)的过程具有很大的优势,即可以利用天然环境中的天然信号级联反应,可能产生质量极高的移植器官。然而,这一方向不可阻挡的科学发展涉及到几个社会问题,因此我们需要提前教育和准备社会,接受这一革命性的后果,无论好坏。

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