诱导多能干细胞在肝脏疾病研究和治疗中的应用

Marc C. Hansel, Julio C. Davila, Massoud Vosough, Roberto Gramignoli, Kristen J. Skvorak, Kenneth Dorko, Fabio Marongiu, William Blake, Stephen C. Strom
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引用次数: 31

摘要

肝病是一个主要的全球健康问题。肝硬化是世界上导致死亡的主要原因之一,目前治疗终末期肝病(如急性肝功能衰竭、肝硬化、慢性肝炎、胆汁淤积性疾病、代谢性疾病和恶性肿瘤)的唯一选择是正异性肝移植。在一些临床病例中,肝细胞移植已被提出并用作整个器官移植的替代方案,以稳定和延长患者的生命。尽管这些实验性疗法已经证明了有希望和有益的结果,但由于可用于细胞分离的供体肝脏短缺、这些组织的质量多变、移植受体可能需要终身免疫抑制以及成本高,它们的常规使用仍然是一个挑战。因此,迫切需要新的治疗策略和更可靠的临床治疗方法。干细胞发展的最新和持续的技术进步表明它们在这方面可能是有益的。在这篇综述中,我们总结了干细胞和诱导多能干细胞(iPSC)技术在肝分化背景下的历史,并讨论了该技术在人类肝脏疾病建模和治疗中的潜在应用。这包括开发更安全的药物和基于细胞的疗法,以改善目前无法治愈的疾病患者的预后。我们还回顾了在其他疾病领域的有希望的进展,以强调干细胞技术在未来如何应用于肝脏疾病。©2016 by John Wiley &儿子,Inc。
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The Use of Induced Pluripotent Stem Cells for the Study and Treatment of Liver Diseases

Liver disease is a major global health concern. Liver cirrhosis is one of the leading causes of death in the world and currently the only therapeutic option for end-stage liver disease (e.g., acute liver failure, cirrhosis, chronic hepatitis, cholestatic diseases, metabolic diseases, and malignant neoplasms) is orthotropic liver transplantation. Transplantation of hepatocytes has been proposed and used as an alternative to whole organ transplant to stabilize and prolong the lives of patients in some clinical cases. Although these experimental therapies have demonstrated promising and beneficial results, their routine use remains a challenge due to the shortage of donor livers available for cell isolation, variable quality of those tissues, the potential need for lifelong immunosuppression in the transplant recipient, and high costs. Therefore, new therapeutic strategies and more reliable clinical treatments are urgently needed. Recent and continuous technological advances in the development of stem cells suggest they may be beneficial in this respect. In this review, we summarize the history of stem cell and induced pluripotent stem cell (iPSC) technology in the context of hepatic differentiation and discuss the potential applications the technology may offer for human liver disease modeling and treatment. This includes developing safer drugs and cell-based therapies to improve the outcomes of patients with currently incurable health illnesses. We also review promising advances in other disease areas to highlight how the stem cell technology could be applied to liver diseases in the future. © 2016 by John Wiley & Sons, Inc.

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