Historical Perspectives and Advances in Mesenchymal Stem Cell Research for the Treatment of Liver Diseases
Historical Perspectives and Advances in Mesenchymal Stem Cell Research for the Treatment of Liver Diseases
复制标题
DOI：
10.1053/j.gastro.2017.09.049
复制
发表时间：
2018-01-01
期刊：
影响因子：
29.4
通讯作者：
Lee, Oscar K.
中科院分区：
文献类型：
--
作者：
Lee, Chien-Wei;Chen, Yu-Fan;Lee, Oscar K.
肝移植是治疗失代偿期肝硬化和暴发性肝功能衰竭的唯一有效方法。然而，由于供体肝脏的短缺和与免疫抑制相关的并发症，迫切需要为终末期肝病患者提供新的治疗策略。鉴于干细胞在自我更新和分化潜能方面的独特功能，干细胞可能用于再生受损的肝组织。最近的研究表明，基于干细胞的疗法可以改善肝衰竭小鼠模型的肝功能。此外，在临床前研究中，用肝细胞接种的脱细胞肝脏支架产生用于器官移植的功能性生物工程肝脏。干细胞或其分化后代的治疗潜力将取决于它们在移植后分化成成熟和功能性细胞类型的能力。同样重要的是设计方法来克服它们的基因组不稳定性、免疫反应性和致瘤潜力。本文综述了间充质干细胞及其衍生肝细胞用于肝再生的研究方向和进展。我们还讨论了来自人多能干细胞的肝细胞的潜在应用以及使用这些细胞治疗终末期肝病的挑战。
Liver transplantation is the only effective therapy for patients with decompensated cirrhosis and fulminant liver failure. However, due to a shortage of donor livers and complications associated with immune suppression, there is an urgent need for new therapeutic strategies for patients with end-stage liver diseases. Given their unique function in self-renewal and differentiation potential, stem cells might be used to regenerate damaged liver tissue. Recent studies have shown that stem cell - based therapies can improve liver function in a mouse model of hepatic failure. Moreover, acellular liver scaffolds seeded with hepatocytes produced functional bioengineered livers for organ transplantation in preclinical studies. The therapeutic potential of stem cells or their differentiated progenies will depend on their capacity to differentiate into mature and functional cell types after transplantation. It will also be important to devise methods to overcome their genomic instability, immune reactivity, and tumorigenic potential. We review directions and advances in the use of mesenchymal stem cells and their derived hepatocytes for liver regeneration. We also discuss the potential applications of hepatocytes derived from human pluripotent stem cells and challenges to using these cells in treating end-stage liver disease.