Clinical Hepatocyte Transplantation: What Is Next?
Clinical Hepatocyte Transplantation: What Is Next?
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DOI：
10.1007/s40472-017-0165-6
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发表时间：
2017-12
影响因子：
2.1
通讯作者：
Soto-Gutierrez A
中科院分区：
文献类型：
--
作者：
Squires JE;Soltys KA;McKiernan P;Squires RH;Strom SC;Fox IJ;Soto-Gutierrez A
近年来在肝脏再生和再生领域取得了重大的科学进展。虽然促进供体肝细胞和不同细胞来源的肝脏再生的技术已经在实验室进行了广泛的研究，但近年来临床肝细胞移植（HT）和肝脏再生试验已经显示出新的疾病适应症和免疫学挑战，这将需要结合新的观点和新的实验方法。生长优势和再生刺激是允许供体肝细胞增殖的必要条件。目前的研究主要集中在供肝细胞扩增对肝损伤/预处理的反应机制上。此外，最新的临床证据表明，HT的重要障碍包括优化植入和有限的有效时间，肝细胞会因免疫排斥而丢失。我们将讨论细胞排斥监测的替代方案，以及跟踪细胞移植功能和接近临床的细胞来源的新模式。HT在有限的时间内部分纠正了遗传性疾病，并与ALF的逆转有关。使HT成为一种治疗方法的主要障碍包括提高移植率，以及监测细胞移植功能和排斥反应的方法。本综述旨在讨论当前临床HT的最新技术，并提供克服这些障碍的创新方法的见解。
Significant recent scientific developments have occurred in the field of liver repopulation and regeneration. While techniques to facilitate liver repopulation with donor hepatocytes and different cell sources have been studied extensively in the laboratory, in recent years clinical hepatocyte transplantation (HT) and liver repopulation trials have demonstrated new disease indications and also immunological challenges that will require the incorporation of a fresh look and new experimental approaches. Growth advantage and regenerative stimulus are necessary to allow donor hepatocytes to proliferate. Current research efforts focus on mechanisms of donor hepatocyte expansion in response to liver injury/preconditioning. Moreover, latest clinical evidence shows that important obstacles to HT include optimizing engraftment and limited duration of effectiveness, with hepatocytes being lost to immunological rejection. We will discuss alternatives for cellular rejection monitoring, as well as new modalities to follow cellular graft function and near-to-clinical cell sources. HT partially corrects genetic disorders for a limited period of time and has been associated with reversal of ALF. The main identified obstacles that remain to make HT a curative approach include improving engraftment rates, and methods for monitoring cellular graft function and rejection. This review aims to discuss current state-of-the-art in clinical HT and provide insights into innovative approaches taken to overcome these obstacles.