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肝细胞移植的临床应用:现状、适用性、局限性和未来展望。

Clinical application of hepatocyte transplantation: current status, applicability, limitations, and future outlook.

机构信息

Dhawan Lab. at the Mowat Labs, Institute of Liver Studies, King's College Hospital, London, United Kingdom.

出版信息

Expert Rev Gastroenterol Hepatol. 2020 Mar;14(3):185-196. doi: 10.1080/17474124.2020.1733975. Epub 2020 Mar 2.

Abstract

: Hepatocyte transplantation (HT) is a promising alternative to liver transplantation for the treatment of liver-based metabolic diseases and acute liver failure (ALF). However, shortage of good-quality liver tissues, early cell loss post-infusion, reduced cell engraftment and function restricts clinical application.: A comprehensive literature search was performed to cover pre-clinical and clinical HT studies. The review discusses the latest developments to address HT limitations: cell sources from marginal/suboptimal donors to neonatal livers, differentiating pluripotent stem cells into hepatocyte-like cells, expansion, prevention of immune response to transplanted cells by encapsulation or using innate immunity-inhibiting agents, and enhancing engraftment through partial hepatectomy or irradiation.: To date, published data are highly encouraging specially the alginate-encapsulated hepatocyte treatment of children with ALF. Hepatocyte functions can be further improved through co-culturing with mesenchymal stromal cells. Moreover, genetic correction will enable the use of autologous cells in future personalized medicine.

摘要

: 肝细胞移植 (HT) 是治疗基于肝脏的代谢性疾病和急性肝衰竭 (ALF) 的一种很有前途的肝移植替代方法。然而,优质肝组织的短缺、输注后早期细胞丢失、细胞植入和功能减少限制了其临床应用。: 进行了全面的文献检索,涵盖了 HT 的临床前和临床研究。本综述讨论了最新的发展,以解决 HT 的局限性:从边缘/次优供体到新生儿肝脏的细胞来源、多能干细胞向肝细胞样细胞的分化、扩增、通过包裹或使用先天免疫抑制剂来防止对移植细胞的免疫反应,以及通过部分肝切除术或辐照来增强植入。: 迄今为止,发表的数据非常令人鼓舞,特别是藻酸盐包封的肝细胞治疗 ALF 儿童的效果。通过与间充质基质细胞共培养,可以进一步改善肝细胞的功能。此外,基因矫正将使未来的个性化医疗能够使用自体细胞。

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