Furuta Tomoaki, Furuya Kinji, Zheng Yun-Wen, Oda Tatsuya
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba-shi 305-8575, Ibaraki, Japan.
World J Transplant. 2020 Mar 31;10(3):64-78. doi: 10.5500/wjt.v10.i3.64.
Orthotopic liver transplantation (OLT) is the only treatment for end-stage liver failure; however, graft shortage impedes its applicability. Therefore, studies investigating alternative therapies are plenty. Nevertheless, no study has comprehensively analyzed these therapies from different perspectives.
To summarize the current status of alternative transplantation therapies for OLT and to support future research.
A systematic literature search was performed using PubMed, Cochrane Library and EMBASE for articles published between January 2010 and 2018, using the following MeSH terms: [(liver transplantation) AND cell] OR [(liver transplantation) AND differentiation] OR [(liver transplantation) AND organoid] OR [(liver transplantation) AND xenotransplantation]. Various types of studies describing therapies to replace OLT were retrieved for full-text evaluation. Among them, we selected articles including transplantation.
A total of 89 studies were selected. There are three principle forms of treatment for liver failure: Xeno-organ transplantation, scaffold-based transplantation, and cell transplantation. Xeno-organ transplantation was covered in 14 articles, scaffold-based transplantation was discussed in 22 articles, and cell transplantation was discussed in 53 articles. Various types of alternative therapies were discussed: Organ liver, 25 articles; adult hepatocytes, 31 articles; fetal hepatocytes, three articles; mesenchymal stem cells (MSCs), 25 articles; embryonic stem cells, one article; and induced pluripotent stem cells, three articles and other sources. Clinical applications were discussed in 12 studies: Cell transplantation using hepatocytes in four studies, five studies using umbilical cord-derived MSCs, three studies using bone marrow-derived MSCs, and two studies using hematopoietic stem cells.
The clinical applications are present only for cell transplantation. Scaffold-based transplantation is a comprehensive treatment combining organ and cell transplantations, which warrants future research to find relevant clinical applications.
原位肝移植(OLT)是终末期肝衰竭的唯一治疗方法;然而,供肝短缺阻碍了其应用。因此,对替代疗法的研究众多。尽管如此,尚无研究从不同角度对这些疗法进行全面分析。
总结OLT替代移植疗法的现状并为未来研究提供支持。
使用PubMed、Cochrane图书馆和EMBASE对2010年1月至2018年发表的文章进行系统文献检索,使用以下医学主题词:[(肝移植) AND 细胞] 或 [(肝移植) AND 分化] 或 [(肝移植) AND 类器官] 或 [(肝移植) AND 异种移植]。检索各种描述替代OLT疗法的研究类型以进行全文评估。其中,我们选择了包括移植的文章。
共选择了89项研究。肝衰竭有三种主要治疗形式:异种器官移植、基于支架的移植和细胞移植。14篇文章涵盖异种器官移植,22篇文章讨论基于支架的移植,53篇文章讨论细胞移植。讨论了各种替代疗法:器官肝,25篇文章;成人肝细胞,31篇文章;胎儿肝细胞,3篇文章;间充质干细胞(MSCs),25篇文章;胚胎干细胞,1篇文章;诱导多能干细胞,3篇文章以及其他来源。12项研究讨论了临床应用:4项研究使用肝细胞进行细胞移植,5项研究使用脐带来源的MSCs,3项研究使用骨髓来源的MSCs,2项研究使用造血干细胞。
仅细胞移植有临床应用。基于支架的移植是一种结合器官和细胞移植的综合治疗方法,值得未来研究以找到相关临床应用。