关键词: blastocyst complementation chimeras end-stage liver disease interspecies blastocyst complementation xenotransplantation

来  源:   DOI:10.2147/HMER.S440697   PDF(Pubmed)

Abstract:
Orthotopic liver transplantation (OLT) currently serves as the sole definitive treatment for thousands of patients suffering from end-stage liver disease; and the existing supply of donor livers for OLT is drastically outpaced by the increasing demand. To alleviate this significant gap in treatment, several experimental approaches have been devised with the aim of either offering interim support to patients waiting on the transplant list or bioengineering complete livers for OLT by infusing them with fresh hepatic cells. Recently, interspecies blastocyst complementation has emerged as a promising method for generating complete organs in utero over a short timeframe. When coupled with gene editing technology, it has brought about a potentially revolutionary transformation in regenerative medicine. Blastocyst complementation harbors notable potential for generating complete human livers in large animals, which could be used for xenotransplantation in humans, addressing the scarcity of livers for OLT. Nevertheless, substantial experimental and ethical challenges still need to be overcome to produce human livers in larger domestic animals like pigs. This review compiles the current understanding of interspecies blastocyst complementation and outlines future possibilities for liver xenotransplantation in humans.
摘要:
原位肝移植(OLT)目前是成千上万患有终末期肝病的患者的唯一最终治疗方法;随着需求的增长,OLT的供体肝脏的现有供应大大超过了。为了缓解这一显著的治疗差距,已经设计了几种实验方法,目的是为等待移植名单的患者提供临时支持,或者通过向OLT输注新鲜肝细胞来生物工程完整肝脏。最近,种间胚泡互补已成为在短时间内在子宫内产生完整器官的有希望的方法。再加上基因编辑技术,它带来了再生医学的潜在革命性转变。囊胚互补具有在大型动物中产生完整人类肝脏的显着潜力,可用于人类异种移植,解决OLT肝脏稀缺的问题。然而,在猪等大型家畜中生产人类肝脏仍然需要克服大量的实验和伦理挑战。这篇综述汇集了当前对种间胚泡互补的理解,并概述了人类肝脏异种移植的未来可能性。
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