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肝细胞治疗:细胞来源和移植策略。

Liver cell therapies: cellular sources and grafting strategies.

机构信息

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

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

出版信息

Front Med. 2023 Jun;17(3):432-457. doi: 10.1007/s11684-023-1002-1. Epub 2023 Jul 4.

DOI:10.1007/s11684-023-1002-1
PMID:37402953
Abstract

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.

摘要

肝脏具有复杂的细胞组成和显著的再生能力。肝脏的主要细胞类型是两种实质细胞群体,肝细胞和胆管细胞,它们执行肝脏的大部分功能,并通过与非实质细胞类型的相互作用得到帮助,这些非实质细胞类型包括星状细胞、内皮细胞和各种造血细胞群体。细胞在肝脏中的调节是由蛋白质和碳水化合物的不溶性复合物,即细胞外基质介导的,与可溶性旁分泌和全身信号协同作用。近年来,随着基因测序技术的快速发展,对各种条件下肝脏的细胞组成及其调节机制的研究已经得到了广泛的探索。同时,细胞移植策略的突破使人们能够拯救终末期肝病患者,为解决慢性肝脏短缺问题提供了潜在的解决方案,并为肝移植提供了替代方案。这篇综述将重点介绍肝脏内稳态的细胞机制,以及如何选择理想的移植细胞来源,以实现肝脏再生和修复。总结了促进细胞移植治疗终末期肝病的最新进展,包括移植策略。

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J Hepatol. 2023 Jan;78(1):165-179. doi: 10.1016/j.jhep.2022.08.037. Epub 2022 Sep 9.
2
Patch grafting of organoids of stem/progenitors into solid organs can correct genetic-based disease states.将干细胞/祖细胞类器官贴片移植到实体器官中可以纠正基于遗传的疾病状态。
Biomaterials. 2022 Sep;288:121647. doi: 10.1016/j.biomaterials.2022.121647. Epub 2022 Aug 7.
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Mouse Models of Liver Parenchyma Injuries and Regeneration.
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Front Genome Ed. 2024 Jun 6;6:1401163. doi: 10.3389/fgeed.2024.1401163. eCollection 2024.
肝脏实质损伤与再生的小鼠模型
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Hepatology. 2022 Dec;76(6):1690-1705. doi: 10.1002/hep.32436. Epub 2022 Mar 22.
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