The multiple functional roles of mesenchymal stem cells in participating in treating liver diseases.
The multiple functional roles of mesenchymal stem cells in participating in treating liver diseases.
复制标题
间充质干细胞参与治疗肝脏疾病的多种功能。
DOI：
10.1111/jcmm.12482
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发表时间：
2015-03
影响因子：
5.3
通讯作者：
Li K
中科院分区：
文献类型：
--
作者：
Liu WH;Song FQ;Ren LN;Guo WQ;Wang T;Feng YX;Tang LJ;Li K
间充质干细胞（MSC）是一组源自中胚层间充质的干细胞。 MSC可以从多种组织中获得，包括骨髓、脐带组织、脐带血、外周血和脂肪组织。在某些条件下，间充质干细胞可以在体外和体内分化成多种细胞类型，包括肝细胞。迄今为止，已开发出四种主要策略来诱导 MSC 转分化为肝细胞：添加化合物和细胞因子、遗传修饰、调整微环境以及改变用于培养 MSC 的物理参数。尽管MSCs转分化为肝细胞的现象已被描述，但详细机制尚不清楚。一般来说，其机制是级联反应，刺激因子激活细胞信号通路，进而促进转录因子的产生，导致肝基因表达。由于间充质干细胞可以产生肝细胞，因此它们有望用作肝功能障碍的新治疗方法或作为肝移植的桥梁。大量研究证实MSCs对肝纤维化、肝硬化等肝脏疾病具有治疗作用，这可能与MSCs分化为功能性肝细胞有关。除了转分化为肝细胞外，间充质干细胞用于治疗肝脏疾病时，还可能抑制肝细胞凋亡，分泌多种生物活性分子，促进肝脏再生。本文对间充质干细胞转分化的能力、分子机制以及间充质干细胞对肝脏疾病的治疗作用进行了深入讨论。
Mesenchymal stem cells (MSCs) are a group of stem cells derived from the mesodermal mesenchyme. MSCs can be obtained from a variety of tissues, including bone marrow, umbilical cord tissue, umbilical cord blood, peripheral blood and adipose tissue. Under certain conditions, MSCs can differentiate into many cell types both in vitro and in vivo, including hepatocytes. To date, four main strategies have been developed to induce the transdifferentiation of MSCs into hepatocytes: addition of chemical compounds and cytokines, genetic modification, adjustment of the micro-environment and alteration of the physical parameters used for culturing MSCs. Although the phenomenon of transdifferentiation of MSCs into hepatocytes has been described, the detailed mechanism is far from clear. Generally, the mechanism is a cascade reaction whereby stimulating factors activate cellular signalling pathways, which in turn promote the production of transcription factors, leading to hepatic gene expression. Because MSCs can give rise to hepatocytes, they are promising to be used as a new treatment for liver dysfunction or as a bridge to liver transplantation. Numerous studies have confirmed the therapeutic effects of MSCs on hepatic fibrosis, cirrhosis and other liver diseases, which may be related to the differentiation of MSCs into functional hepatocytes. In addition to transdifferentiation into hepatocytes, when MSCs are used to treat liver disease, they may also inhibit hepatocellular apoptosis and secrete various bioactive molecules to promote liver regeneration. In this review, the capacity and molecular mechanism of MSC transdifferentiation, and the therapeutic effects of MSCs on liver diseases are thoroughly discussed.
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