肝細(xì)胞療法：細(xì)胞來(lái)源與移植策略

導(dǎo) 讀

北卡羅來(lái)納大學(xué)醫(yī)學(xué)院Lola M. Reid博士和同濟(jì)大學(xué)生命科學(xué)與技術(shù)學(xué)院何志穎研究員等在Frontiers of Medicine發(fā)表綜述論文《肝細(xì)胞療法：細(xì)胞來(lái)源與移植策略》（Liver cell therapies: cellular sources and grafting strategies）。本綜述梳理了不同條件下參與肝臟修復(fù)的細(xì)胞的最新研究進(jìn)展，旨在為終末期肝病提供有效的干預(yù)措施。

The liver has a complex cellular composition and a remarkable regenerative capacity. The primary cell types in the liver are two parenchymal cell populations, hepatocytes and cholangiocytes, that perform most of the functions of the liver and that are helped through interactions with non-parenchymal cell types comprising stellate cells, endothelia and various hemopoietic cell populations. The regulation of the cells in the liver is mediated by an insoluble complex of proteins and carbohydrates, the extracellular matrix, working synergistically with soluble paracrine and systemic signals. In recent years, with the rapid development of genetic sequencing technologies, research on the liver’s cellular composition and its regulatory mechanisms during various conditions has been extensively explored. Meanwhile breakthroughs in strategies for cell transplantation are enabling a future in which there can be a rescue of patients with end-stage liver diseases, offering potential solutions to the chronic shortage of livers and alternatives to liver transplantation. This review will focus on the cellular mechanisms of liver homeostasis and how to select ideal sources of cells to be transplanted to achieve liver regeneration and repair. Recent advances are summarized for promoting the treatment of end-stage liver diseases by forms of cell transplantation that now include grafting strategies.

肝臟具有復(fù)雜的細(xì)胞組成和卓越的再生能力。肝臟中的主要細(xì)胞類(lèi)型為兩種實(shí)質(zhì)細(xì)胞群，即肝細(xì)胞和膽管細(xì)胞，它們承擔(dān)了肝臟的大部分功能，并通過(guò)與非實(shí)質(zhì)細(xì)胞（包括星狀細(xì)胞、內(nèi)皮細(xì)胞和各種造血細(xì)胞群）的相互作用發(fā)揮協(xié)同作用。肝臟細(xì)胞的調(diào)控由蛋白質(zhì)和碳水化合物構(gòu)成的不溶性復(fù)合物——細(xì)胞外基質(zhì)介導(dǎo)，并與可溶性旁分泌信號(hào)和全身信號(hào)協(xié)同作用。近年來(lái)，隨著基因測(cè)序技術(shù)的快速發(fā)展，關(guān)于肝臟細(xì)胞組成及其在不同狀態(tài)下調(diào)控機(jī)制的研究得到了廣泛探索。同時(shí)，細(xì)胞移植策略取得突破，為挽救終末期肝病患者帶來(lái)了希望，為解決肝臟長(zhǎng)期短缺問(wèn)題提供了潛在解決方案，并有望成為肝移植的替代方法。本文將重點(diǎn)探討肝臟穩(wěn)態(tài)的細(xì)胞機(jī)制，以及如何選擇理想的移植細(xì)胞來(lái)源以實(shí)現(xiàn)肝臟再生和修復(fù)。本文還總結(jié)了通過(guò)細(xì)胞移植（包括移植策略）促進(jìn)終末期肝病治療的最新進(jìn)展。

原文信息

標(biāo)題

Liver cell therapies: cellular sources and grafting strategies

作者

Wencheng Zhang1,2,3, Yangyang Cui1,2,3,4, Yuan Du1,5, Yong Yang1,5, Ting Fang1,2,3, Fengfeng Lu1,2,3, Weixia Kong6, Canjun Xiao7, Jun Shi5,7, Lola M. Reid8, Zhiying He1,2,3

機(jī)構(gòu)

1. Institute for Regenerative Medicine, Ji’an Hospital, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200123, China

2. Shanghai Engineering Research Center of Stem Cells Translational Medicine, Shanghai 200335, China

3. Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai 200120, China

4. Postgraduate Training Base of Shanghai East Hospital, Jinzhou Medical University, Jinzhou 121001, China

5. The First Affiliated Hospital of Nanchang University, Nanchang 330006, China

6. Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, 565-0871, Japan

7. Department of General Surgery, Ji’an Hospital, Shanghai East Hospital, School of Medicine, Tongji University, Ji’an 343006, China

8. Department of Cell Biology and Physiology and Program in Molecular Biology and Biotechnology; UNC School of Medicine, Chapel Hill, NC 27599, USA

通訊作者

Lola M. Reid, Zhiying He