Nicolas Clara T, Wang Yujia, Nyberg Scott L
aWilliam J. von Liebig Center for Transplantation and Clinical RegenerationbDepartment of Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Curr Opin Gastroenterol. 2016 May;32(3):189-94. doi: 10.1097/MOG.0000000000000262.
To date, the only curative treatment for end-stage liver disease is liver transplantation, which is limited by the shortage of available organs. Cell therapy, in the form of cell transplantation or cell-based extracorporeal support devices, may in the future offer an alternative to transplantation, or at least provide liver function support as a bridging therapy until surgery may be performed. The purpose of this review is to highlight the most recent advances made in the field of cell therapy and regenerative medicine for the treatment of chronic liver disease.
After hepatocyte transplantation, long-term engraftment in the liver and spleen may be achieved, which can be stimulated through preconditioning, multiple infusions, and inflammatory response blockade. Mesenchymal stem cells are promising candidates for cell transplantation, as they have been shown to reduce liver fibrosis and support endogenous regeneration. Adipose tissue-derived stem cells are also being tested in this setting, because of their ready availability. Bioartificial liver devices are being built that allow for effective preservation of hepatocytes, and one such device has recently demonstrated survival benefit in a porcine model of liver failure.
Cell transplantation of primary hepatocytes or stem cell-derived hepatocyte-like cells for the treatment of chronic liver disease holds promise. Bioartificial liver systems may in the future be able to bridge acute-on-chronic liver failure patients to liver transplantation.
迄今为止,终末期肝病的唯一治愈性治疗方法是肝移植,但受可用器官短缺的限制。细胞疗法,无论是细胞移植形式还是基于细胞的体外支持装置,未来可能为移植提供替代方案,或者至少作为一种桥接疗法提供肝功能支持,直至能够进行手术。本综述的目的是突出细胞疗法和再生医学领域在治疗慢性肝病方面取得的最新进展。
肝细胞移植后,可在肝脏和脾脏中长期植入,通过预处理、多次输注和炎症反应阻断可促进植入。间充质干细胞是细胞移植的有前景的候选者,因为它们已被证明可减少肝纤维化并支持内源性再生。脂肪组织来源的干细胞也正在此背景下进行测试,因其易于获取。正在构建能够有效保存肝细胞的生物人工肝装置,并且其中一种装置最近在猪肝衰竭模型中显示出生存获益。
原代肝细胞或干细胞来源的类肝细胞的细胞移植治疗慢性肝病具有前景。生物人工肝系统未来可能能够将慢加急性肝衰竭患者过渡到肝移植。