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成人肝脏中的间充质干细胞:炒作还是希望?

Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope?

机构信息

Orekhovich Institute of Biomedical Chemistry, 10, Pogodinskaya St., 119121 Moscow, Russia.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho- Maklaya St., 117997 Moscow, Russia.

出版信息

Cells. 2019 Sep 22;8(10):1127. doi: 10.3390/cells8101127.

DOI:10.3390/cells8101127
PMID:31546729
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6830330/
Abstract

Chronic liver diseases constitute a significant economic, social, and biomedical burden. Among commonly adopted approaches, only organ transplantation can radically help patients with end-stage liver pathologies. Cell therapy with hepatocytes as a treatment for chronic liver disease has demonstrated promising results. However, quality human hepatocytes are in short supply. Stem/progenitor cells capable of differentiating into functionally active hepatocytes provide an attractive alternative approach to cell therapy for liver diseases, as well as to liver-tissue engineering, drug screening, and basic research. The application of methods generally used to isolate mesenchymal stem cells (MSCs) and maintain them in culture to human liver tissue provides cells, designated here as liver MSCs. They have much in common with MSCs from other tissues, but differ in two aspects-expression of a range of hepatocyte-specific genes and, possibly, inherent commitment to hepatogenic differentiation. The aim of this review is to analyze data regarding liver MSCs, probably another type of liver stem/progenitor cells different from hepatic stellate cells or so-called hepatic progenitor cells. The review presents an analysis of the phenotypic characteristics of liver MSCs, their differentiation and therapeutic potential, methods for isolating these cells from human liver, and discusses issues of their origin and heterogeneity. Human liver MSCs are a fascinating object of fundamental research with a potential for important practical applications.

摘要

慢性肝脏疾病构成了重大的经济、社会和生物医学负担。在常用的方法中,只有器官移植才能从根本上帮助患有终末期肝脏疾病的患者。肝细胞作为治疗慢性肝脏疾病的细胞疗法已经显示出了很有前景的结果。然而,高质量的人类肝细胞供应不足。具有分化为功能活跃的肝细胞能力的干细胞/祖细胞为肝脏疾病的细胞疗法、肝脏组织工程、药物筛选和基础研究提供了一种有吸引力的替代方法。通常用于分离间充质干细胞(MSCs)并在培养中维持其功能的方法应用于人类肝脏组织,提供了被称为肝间充质干细胞的细胞。它们与来自其他组织的 MSCs 有很多共同之处,但在两个方面有所不同——表达一系列肝细胞特异性基因,并且可能具有向肝细胞分化的固有倾向。本综述的目的是分析关于肝间充质干细胞的数据,这些细胞可能是另一种不同于肝星状细胞或所谓的肝祖细胞的肝干细胞/祖细胞。本综述分析了肝间充质干细胞的表型特征、它们的分化和治疗潜力、从人类肝脏中分离这些细胞的方法,并讨论了它们的起源和异质性问题。人肝间充质干细胞是基础研究的一个引人入胜的对象,具有重要的实际应用潜力。

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Clinical Protocol to Prevent Thrombogenic Effect of Liver-Derived Mesenchymal Cells for Cell-Based Therapies.临床方案以预防基于细胞的治疗中肝源间充质细胞的血栓形成效应。
Cells. 2019 Aug 7;8(8):846. doi: 10.3390/cells8080846.
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The Immunomodulatory Functions of Mesenchymal Stromal/Stem Cells Mediated via Paracrine Activity.间充质基质/干细胞通过旁分泌活性介导的免疫调节功能。
J Clin Med. 2019 Jul 12;8(7):1025. doi: 10.3390/jcm8071025.
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Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs.
细胞外囊泡生物制造的进展:大规模生产与临床研究综述
Front Bioeng Biotechnol. 2025 Feb 19;13:1487627. doi: 10.3389/fbioe.2025.1487627. eCollection 2025.
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Human Liver MSCs Retain Their Basic Cellular Properties in Chronically Inflamed Liver Tissue.人肝间充质干细胞在慢性炎症肝组织中保留其基本细胞特性。
Int J Mol Sci. 2024 Dec 13;25(24):13374. doi: 10.3390/ijms252413374.
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Mesenchymal stromal cell-derived extracellular vesicles therapy openings new translational challenges in immunomodulating acute liver inflammation.间质基质细胞衍生的细胞外囊泡治疗为免疫调节急性肝炎症带来新的转化挑战。
J Transl Med. 2024 May 21;22(1):480. doi: 10.1186/s12967-024-05282-9.
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Enhancing Spermatogenesis in Non-obstructive Azoospermia Through Mesenchymal Stem Cell Therapy22.通过间充质干细胞治疗增强非梗阻性无精子症中的精子发生 22.
Curr Stem Cell Res Ther. 2024;19(11):1429-1441. doi: 10.2174/011574888X283311231226081845.
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