Haridass Dhivya, Narain Nidhi, Ott Michael
Clinic for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Curr Opin Organ Transplant. 2008 Dec;13(6):627-32. doi: 10.1097/MOT.0b013e328317a44f.
Hepatocyte transplantation has been proposed as an attractive therapeutic approach to a variety of liver diseases. Progress, however, in several areas is needed, before this form of therapy is broadly accepted and applied to patients with liver disease. The purpose of the review is to provide the reader with the latest scientific developments relevant for future liver cell therapies.
Clinical application of hepatocyte transplantation is limited by good quality donor livers for the isolation of cells. Recent publications thus focus on stem cells as suitable sources for hepatocytes and liver repopulation strategies that could reduce the number of transplanted cells. How to overcome host immune responses against allogeneic cells can potentially be learned from a new tolerance protocol. Recently discovered technologies for reprogramming of postnatal cells into pluripotent stem cells may pave the way towards the generation of patient-specific autologous cells.
The current focus of research aims to reduce the shortage of transplantable cells by the application of stem cell sources or by the conditioning of recipient livers. Therapies for severe chronic liver diseases based on adult (stem) cells are already beginning to move into clinical trials. However, many questions about safety and efficacy need to be answered, before fetal liver progenitor cells, embryonic stem cells and induced pluripotent stem cells can be applied in humans.
肝细胞移植已被提议作为治疗多种肝脏疾病的一种有吸引力的方法。然而,在这种治疗形式被广泛接受并应用于肝病患者之前,在几个方面仍需取得进展。本综述的目的是为读者提供与未来肝细胞治疗相关的最新科学进展。
肝细胞移植的临床应用受到用于分离细胞的优质供体肝脏的限制。因此,最近的出版物集中于将干细胞作为肝细胞的合适来源以及可减少移植细胞数量的肝脏再填充策略。如何克服宿主对异体细胞的免疫反应可能可以从一种新的耐受方案中学习。最近发现的将出生后细胞重编程为多能干细胞的技术可能为生成患者特异性自体细胞铺平道路。
当前的研究重点旨在通过应用干细胞来源或通过对受体肝脏进行预处理来减少可移植细胞的短缺。基于成人(干)细胞的严重慢性肝病治疗已经开始进入临床试验。然而,在胎儿肝祖细胞、胚胎干细胞和诱导多能干细胞能够应用于人类之前,许多关于安全性和有效性的问题需要得到解答。