Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.
Department of Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.
Int J Radiat Oncol Biol Phys. 2019 Mar 15;103(4):922-934. doi: 10.1016/j.ijrobp.2018.11.016. Epub 2018 Nov 29.
Orthotopic liver transplantation (OLT) has been effective in managing end-stage liver disease since the advent of cyclosporine immunosuppression therapy in 1980. The major limitations of OLT are organ supply, monetary cost, and the burden of lifelong immunosuppression. Hepatocyte transplantation, as a substitute for OLT, has been an exciting topic of investigation for several decades. HT is potentially minimally invasive and can serve as a vehicle for delivery of personalized medicine through autologous cell transplant after modification ex vivo. However, 3 major hurdles have prevented large-scale clinical application: (1) availability of transplantable cells; (2) safe and efficient ex vivo gene therapy methods; and (3) engraftment and repopulation efficiency. This review will discuss new sources for transplantable liver cells obtained by lineage reprogramming, clinically acceptable methods of genetic manipulation, and the development of hepatic irradiation-based preparative regimens for enhancing engraftment and repopulation of transplanted hepatocytes. We will also review the results of the first 3 patients with genetic liver disorders who underwent preparative hepatic irradiation before hepatocyte transplantation.
自 1980 年环孢素免疫抑制疗法问世以来，原位肝移植（OLT）已成为治疗终末期肝病的有效方法。OLT 的主要限制因素包括器官供应、经济成本和终身免疫抑制的负担。几十年来，肝细胞移植作为 OLT 的替代方法一直是一个令人兴奋的研究课题。HT 具有潜在的微创性，可以通过自体细胞移植在体外修饰后作为传递个体化药物的载体。然而，有 3 大障碍阻止了其大规模临床应用：（1）可移植细胞的可用性；（2）安全有效的体外基因治疗方法；以及（3）植入和再殖效率。这篇综述将讨论通过谱系重编程获得可移植肝细胞的新来源、临床可接受的遗传操作方法，以及开发基于肝脏照射的预备方案以提高移植肝细胞的植入和再殖效率。我们还将回顾前 3 例接受肝细胞移植前肝脏照射预备治疗的遗传性肝病患者的结果。
