Meier Raphael P H, Müller Yannick D, Morel Philippe, Gonelle-Gispert Carmen, Bühler Leo H
Surgical Research Unit, Transplantation and Visceral Surgery, University Hospital and Medical Faculty, Geneva, Switzerland.
Stem Cell Res. 2013 Nov;11(3):1348-64. doi: 10.1016/j.scr.2013.08.011. Epub 2013 Aug 29.
Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) have been extensively investigated in small animal models to treat both acute and chronic liver injuries. Mechanisms of action are not clearly elucidated but may include their ability to differentiate into hepatocyte-like cells, to reduce inflammation, and to enhance tissue repair at the site of injury. This approach is controversial and evidence in large animals is missing. Side effects of MSC infusion such as the contribution to a fibrotic process have been reported in experimental settings. Nevertheless, MSCs moved quickly from bench to bedside and over 280 clinical trials are registered, of which 28 focus on the treatment of liver diseases. If no severe side-effects were observed so far, long-term benefits remain uncertain. More preclinical data regarding mechanisms of action, long term safety and efficacy are warranted before initiating large scale clinical application. The proposal of this review is to visit the current state of knowledge regarding mechanisms behind the therapeutic effects of MSCs in the treatment of experimental liver diseases, to address questions about efficacy and risk, and to discuss recent clinical advances involving MSC-based therapies.
间充质干细胞或多能间充质基质细胞(MSCs)已在小动物模型中被广泛研究用于治疗急性和慢性肝损伤。其作用机制尚未完全阐明,但可能包括分化为肝细胞样细胞的能力、减轻炎症以及增强损伤部位的组织修复。这种方法存在争议,且缺乏大型动物实验的证据。在实验环境中已报道了MSC输注的副作用,如对纤维化过程的影响。尽管如此,MSCs已迅速从实验室走向临床,目前已注册超过280项临床试验,其中28项聚焦于肝脏疾病的治疗。虽然目前尚未观察到严重的副作用,但其长期益处仍不确定。在启动大规模临床应用之前,需要更多关于作用机制、长期安全性和有效性的临床前数据。本综述的目的是探讨目前关于MSCs治疗实验性肝病的治疗效果背后机制的知识现状,解决有关疗效和风险的问题,并讨论基于MSCs治疗的最新临床进展。