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间质基质细胞:肝硬化有希望的治疗方法。

Mesenchymal stromal cells: promising treatment for liver cirrhosis.

机构信息

Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.

出版信息

Stem Cell Res Ther. 2022 Jul 15;13(1):308. doi: 10.1186/s13287-022-03001-z.

Abstract

Liver fibrosis is a wound-healing process that occurs in response to severe injuries and is hallmarked by the excessive accumulation of extracellular matrix or scar tissues within the liver. Liver fibrosis can be either acute or chronic and is induced by a variety of hepatotoxic causes, including lipid deposition, drugs, viruses, and autoimmune reactions. In advanced fibrosis, liver cirrhosis develops, a condition for which there is no successful therapy other than liver transplantation. Although liver transplantation is still a viable option, numerous limitations limit its application, including a lack of donor organs, immune rejection, and postoperative complications. As a result, there is an immediate need for a different kind of therapeutic approach. Recent research has shown that the administration of mesenchymal stromal cells (MSCs) is an attractive treatment modality for repairing liver injury and enhancing liver regeneration. This is accomplished through the cell migration into liver sites, immunoregulation, hepatogenic differentiation, as well as paracrine mechanisms. MSCs can also release a huge variety of molecules into the extracellular environment. These molecules, which include extracellular vesicles, lipids, free nucleic acids, and soluble proteins, exert crucial roles in repairing damaged tissue. In this review, we summarize the characteristics of MSCs, representative clinical study data, and the potential mechanisms of MSCs-based strategies for attenuating liver cirrhosis. Additionally, we examine the processes that are involved in the MSCs-dependent modulation of the immune milieu in liver cirrhosis. As a result, our findings lend credence to the concept of developing a cell therapy treatment for liver cirrhosis that is premised on MSCs. MSCs can be used as a candidate therapeutic agent to lengthen the survival duration of patients with liver cirrhosis or possibly reverse the condition in the near future.

摘要

肝纤维化是一种创伤愈合过程,发生于严重损伤时,其特征是肝内细胞外基质或疤痕组织的过度积累。肝纤维化可以是急性的也可以是慢性的,由多种肝毒性原因引起,包括脂质沉积、药物、病毒和自身免疫反应。在晚期纤维化中,发展为肝硬化,除了肝移植,目前尚无有效的治疗方法。尽管肝移植仍然是一种可行的选择,但许多限制限制了其应用,包括供体器官缺乏、免疫排斥和术后并发症。因此,迫切需要一种不同的治疗方法。最近的研究表明,间充质基质细胞(MSCs)的给药是修复肝损伤和增强肝再生的一种有吸引力的治疗方式。这是通过细胞迁移到肝部位、免疫调节、肝向分化以及旁分泌机制来实现的。MSCs 还可以将大量不同的分子释放到细胞外环境中。这些分子包括细胞外囊泡、脂质、游离核酸和可溶性蛋白,在修复受损组织中发挥关键作用。在这篇综述中,我们总结了 MSCs 的特征、有代表性的临床研究数据以及基于 MSCs 的策略减轻肝硬化的潜在机制。此外,我们还研究了 MSCs 依赖调节肝硬化免疫微环境的过程。因此,我们的发现为基于 MSCs 的肝硬化细胞治疗提供了可信度。MSCs 可以用作候选治疗剂,延长肝硬化患者的生存时间,或者在不久的将来可能逆转病情。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e38b/9284869/a19d3e414126/13287_2022_3001_Fig1_HTML.jpg

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