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间质干细胞/基质细胞在肝纤维化中的作用:最新发现、旧/新警示及未来展望。

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives.

机构信息

Gene Therapy Laboratory, Liver Unit, School of Medicine, Austral University, Av. Presidente Perón, B1629ODT, Derqui-Pilar, Buenos Aires, Argentina.

出版信息

Stem Cell Rev Rep. 2015 Aug;11(4):586-97. doi: 10.1007/s12015-015-9585-9.

DOI:10.1007/s12015-015-9585-9
PMID:25820543
Abstract

Mesenchymal stem/stromal cells (MSCs) are progenitors which share plastic-adherence capacity and cell surface markers but have different properties according to their cell and tissue sources and to culture conditions applied. Many recent publications suggest that MSCs can differentiate into hepatic-like cells, which can be a consequence of either a positive selection of rare in vivo pluripotent cells or of the original plasticity of some cells contributing to MSC cultures. A possible role of MSCs in hereditary transmission of obesity and/or diabetes as well as properties of MSCs regarding immunomodulation, cell fusion and exosome release capacities are discussed according to recent literature. Limitations in methods used to track MSCs in vivo especially in the context of liver cirrhosis are addressed as well as strategies explored to enhance their migratory, survival and proliferation properties, which are known to be relevant for their future clinical use. Current knowledge regarding mechanisms involved in liver cirrhosis amelioration mediated by naïve and genetically modified MSCs as well as the effects of applying preconditioning and combined strategies to improve their therapeutic effects are evaluated. Finally, first reports of GMP guidelines and biosafety issues in MSCs applications are discussed.

摘要

间充质干细胞(MSCs)是具有多向分化潜能的干细胞,其具有自我更新和多向分化的能力,根据其来源和培养条件的不同,其特性也有所不同。最近的许多研究表明,MSCs 可以分化为肝样细胞,这可能是由于体内稀有多能细胞的阳性选择,也可能是由于一些参与 MSC 培养的细胞的原始可塑性所致。根据最近的文献,探讨了 MSCs 在肥胖和/或糖尿病的遗传传递中的可能作用以及 MSCs 关于免疫调节、细胞融合和外泌体释放能力的特性。还讨论了在体内追踪 MSCs 时所使用的方法的局限性,特别是在肝硬化的情况下,以及探索增强其迁移、存活和增殖特性的策略,这些策略与它们的未来临床应用有关。评估了 MSC 介导的肝硬化改善相关的机制、未经修饰和基因修饰的 MSC 的效果以及预处理和联合策略的应用对提高治疗效果的影响。最后,讨论了 MSCs 应用的 GMP 指南和生物安全性问题的初步报告。

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Viruses. 2024 Nov 17;16(11):1785. doi: 10.3390/v16111785.
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本文引用的文献

1
How important is differentiation in the therapeutic effect of mesenchymal stromal cells in liver disease?间充质基质细胞在肝病治疗效果中的分化作用有多重要?
Cytotherapy. 2014 Mar;16(3):309-18. doi: 10.1016/j.jcyt.2013.07.011. Epub 2013 Nov 13.
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The therapeutic potential of bone marrow-derived mesenchymal stromal cells on hepatocellular carcinoma.骨髓间充质基质细胞对肝细胞癌的治疗潜力
Liver Int. 2014 Mar;34(3):330-42. doi: 10.1111/liv.12338. Epub 2013 Oct 21.
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Mesenchymal stromal cells: sensors and switchers of inflammation.
IMT504 的抗纤维化潜力:调节 GLAST+Wnt1+骨髓基质祖细胞和肝微环境。
Stem Cell Res Ther. 2024 Sep 4;15(1):278. doi: 10.1186/s13287-024-03896-w.
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Effectiveness of human adipose tissue-derived mesenchymal stem cells expressing alpha-1 antitrypsin gene in liver fibrosis: a study in mice.表达α-1抗胰蛋白酶基因的人脂肪组织来源间充质干细胞在肝纤维化中的有效性:一项小鼠研究
Gastroenterol Hepatol Bed Bench. 2024;17(2):151-160. doi: 10.22037/ghfbb.v17i2.2923.
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Modified mesenchymal stromal cells by in vitro transcribed mRNA: a therapeutic strategy for hepatocellular carcinoma.经体外转录 mRNA 修饰的间充质基质细胞:肝细胞癌的治疗策略。
Stem Cell Res Ther. 2024 Jul 11;15(1):208. doi: 10.1186/s13287-024-03806-0.
6
Exosomes derived from adipose tissue-derived stem cells alleviated HO-induced oxidative stress and endothelial-to-mesenchymal transition in human umbilical vein endothelial cells by inhibition of the mir-486-3p/Sirt6/Smad signaling pathway.脂肪组织来源的干细胞衍生的外泌体通过抑制 mir-486-3p/Sirt6/Smad 信号通路缓解了 HO 诱导的人脐静脉内皮细胞氧化应激和内皮到间充质转化。
Cell Biol Toxicol. 2024 May 25;40(1):39. doi: 10.1007/s10565-024-09881-6.
7
Chromatographic Scalable Method to Isolate Engineered Extracellular Vesicles Derived from Mesenchymal Stem Cells for the Treatment of Liver Fibrosis in Mice.色谱可扩展方法分离间充质干细胞来源的工程细胞外囊泡,用于治疗小鼠肝纤维化。
Int J Mol Sci. 2023 May 31;24(11):9586. doi: 10.3390/ijms24119586.
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ADSCs-derived exosomes ameliorate hepatic fibrosis by suppressing stellate cell activation and remodeling hepatocellular glutamine synthetase-mediated glutamine and ammonia homeostasis.脂肪间充质干细胞来源的外泌体通过抑制肝星状细胞活化和重塑肝细胞谷氨酰胺合成酶介导的谷氨酰胺和氨内稳态来改善肝纤维化。
Stem Cell Res Ther. 2022 Oct 4;13(1):494. doi: 10.1186/s13287-022-03049-x.
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Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Agent for the Treatment of Liver Diseases.间质干细胞衍生的外泌体:治疗肝脏疾病的有前途的治疗剂。
Int J Mol Sci. 2022 Sep 19;23(18):10972. doi: 10.3390/ijms231810972.
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The Role of Exosomes in Viral Hepatitis and Its Associated Liver Diseases.外泌体在病毒性肝炎及其相关肝脏疾病中的作用
Front Med (Lausanne). 2021 Nov 22;8:782485. doi: 10.3389/fmed.2021.782485. eCollection 2021.
间质基质细胞:炎症的传感器和开关。
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M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway.M2 样巨噬细胞通过甘露糖受体介导的途径负责胶原蛋白的降解。
J Cell Biol. 2013 Sep 16;202(6):951-66. doi: 10.1083/jcb.201301081. Epub 2013 Sep 9.
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Human placenta-derived mesenchymal stem cells promote hepatic regeneration in CCl4 -injured rat liver model via increased autophagic mechanism.人胎盘源间充质干细胞通过增加自噬机制促进 CCl4 损伤大鼠肝模型的肝再生。
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Mesenchymal stem cells and Interleukin-6 attenuate liver fibrosis in mice.间质干细胞和白细胞介素 6 可减轻小鼠肝纤维化。
J Transl Med. 2013 Mar 26;11:78. doi: 10.1186/1479-5876-11-78.
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Recovery of the Cell Cycle Inhibition in CCl(4)-Induced Cirrhosis by the Adenosine Derivative IFC-305.腺苷衍生物IFC-305对四氯化碳诱导的肝硬化细胞周期抑制的恢复作用
Int J Hepatol. 2012;2012:212530. doi: 10.1155/2012/212530. Epub 2012 Sep 27.
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Mesenchymal stem cells restore CCl4-induced liver injury by an antioxidative process.间充质干细胞通过抗氧化过程恢复 CCl4 诱导的肝损伤。
Cell Biol Int. 2012;36(12):1267-74. doi: 10.1042/CBI20110634.
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Transplanted human amniotic membrane-derived mesenchymal stem cells ameliorate carbon tetrachloride-induced liver cirrhosis in mouse.人羊膜间充质干细胞移植改善小鼠四氯化碳诱导的肝纤维化。
PLoS One. 2011 Feb 4;6(2):e16789. doi: 10.1371/journal.pone.0016789.
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Liver fibrosis.肝纤维化
J Clin Invest. 2005 Feb;115(2):209-18. doi: 10.1172/JCI24282.