Liver-Regenerative Transplantation: Regrow and Reset.
Liver-Regenerative Transplantation: Regrow and Reset.
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DOI：
10.1111/ajt.13678
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Soto-Gutierrez A
中科院分区：
文献类型：
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作者：
Collin de l'Hortet A;Takeishi K;Guzman-Lepe J;Handa K;Matsubara K;Fukumitsu K;Dorko K;Presnell SC;Yagi H;Soto-Gutierrez A
肝移植，无论是从活体或已故供体的部分肝脏还是从已故供体的整个肝脏，都是严重终末期肝病的唯一治愈性疗法。肝脏移植等候名单上只有三分之一的人会接受移植，预计未来20年对肝脏的需求将增加23%。因此，器官可用性是对可以进行的肝脏移植数量的绝对限制。再生疗法旨在通过任何可用的手段（细胞再生、组织工程、生物材料、蛋白质、小分子和基因）来增强肝组织修复和再生。最近的实验工作表明，如果可以实现功能性诱导多能干细胞（iPS）衍生的肝细胞的无限可用性，则肝脏再生和工程化肝组织最适合于该任务。通过重编程细胞命运衍生iPS细胞开辟了新的研究方向，例如，iPS衍生的异种器官的产生或简单诱导肝脏在损伤后重编程其自身肝细胞功能的可能性。本文综述了目前有关肝再生、工程肝的产生和肝功能重编程的知识。我们还讨论了临床实施必须克服的许多障碍。
Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end-stage liver disease. Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes). Recent experimental work suggests that liver repopulation and engineered liver tissue are best suited to the task if an unlimited availability of functional induced pluripotent stem (iPS)–derived liver cells can be achieved. The derivation of iPS cells by reprogramming cell fate has opened up new lines of investigation, for instance, the generation of iPS-derived xenogeneic organs or the possibility of simply inducing the liver to reprogram its own hepatocyte function after injury. We reviewed current knowledge about liver repopulation, generation of engineered livers and reprogramming of liver function. We also discussed the numerous barriers that have to be overcome for clinical implementation.