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实验性肝细胞异种移植——文献综述

Experimental hepatocyte xenotransplantation--a comprehensive review of the literature.

作者信息

Zhou Huidong, Liu Hong, Ezzelarab Mohamed, Schmelzer Eva, Wang Yi, Gerlach Jörg, Gridelli Bruno, Cooper David K C

机构信息

Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.

Center for Kidney Transplantation, Second Affiliated Hospital of the University of South China, Hengyang, Hunan, China.

出版信息

Xenotransplantation. 2015 Jul-Aug;22(4):239-48. doi: 10.1111/xen.12170. Epub 2015 May 7.

Abstract

Hepatocyte transplantation (Tx) is a potential therapy for certain diseases of the liver, including hepatic failure. However, there is a limited supply of human livers as a source of cells and, after isolation, human hepatocytes can be difficult to expand in culture, limiting the number available for Tx. Hepatocytes from other species, for example, the pig, have therefore emerged as a potential alternative source. We searched the literature through the end of 2014 to assess the current status of experimental research into hepatocyte xenoTx. The literature search identified 51 reports of in vivo cross-species Tx of hepatocytes in a variety of experimental models. Most studies investigated the Tx of human (n = 23) or pig (n = 19) hepatocytes. No studies explored hepatocytes from genetically engineered pigs. The spleen was the most common site of Tx (n = 23), followed by the liver (through the portal vein [n = 6]) and peritoneal cavity (n = 19). In 47 studies (92%), there was evidence of hepatocyte engraftment and function across a species barrier. The data provided by this literature search strengthen the hypothesis that xenoTx of hepatocytes is feasible and potentially successful as a clinical therapy for certain liver diseases, including hepatic failure. By excluding vascular structures, hepatocytes isolated from genetically engineered pig livers may address some of the immunological problems of xenoTx.

摘要

肝细胞移植(Tx)是治疗某些肝脏疾病(包括肝衰竭)的一种潜在疗法。然而,作为细胞来源的人类肝脏供应有限,并且在分离后,人类肝细胞在培养中可能难以扩增,这限制了可用于移植的细胞数量。因此,来自其他物种(例如猪)的肝细胞已成为一种潜在的替代来源。我们检索了截至2014年底的文献,以评估肝细胞异种移植的实验研究现状。文献检索确定了51篇关于在各种实验模型中进行肝细胞体内跨物种移植的报告。大多数研究调查了人类(n = 23)或猪(n = 19)肝细胞的移植。没有研究探索来自基因工程猪的肝细胞。脾脏是最常见的移植部位(n = 23),其次是肝脏(通过门静脉[n = 6])和腹腔(n = 19)。在47项研究(92%)中,有证据表明肝细胞能够跨越物种屏障实现植入并发挥功能。该文献检索提供的数据强化了这样一种假设,即肝细胞异种移植作为治疗某些肝脏疾病(包括肝衰竭)的临床疗法是可行的,并且可能会取得成功。通过去除血管结构,从基因工程猪肝脏中分离的肝细胞可能会解决异种移植的一些免疫问题。

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