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临床肝细胞移植:下一步是什么?

Clinical Hepatocyte Transplantation: What Is Next?

作者信息

Squires James E, Soltys Kyle A, McKiernan Patrick, Squires Robert H, Strom Stephen C, Fox Ira J, Soto-Gutierrez Alejandro

机构信息

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Thomas E. Starzl Transplant Institute, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

出版信息

Curr Transplant Rep. 2017 Dec;4(4):280-289. doi: 10.1007/s40472-017-0165-6. Epub 2017 Oct 14.

Abstract

PURPOSE OF REVIEW

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.

RECENT FINDINGS

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.

SUMMARY

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.

摘要

综述目的

肝脏再填充与再生领域最近取得了重大科学进展。虽然在实验室中已对促进供体肝细胞和不同细胞来源进行肝脏再填充的技术进行了广泛研究,但近年来临床肝细胞移植(HT)和肝脏再填充试验已证明了新的疾病适应症以及免疫挑战,这将需要采用全新视角和新的实验方法。

最新发现

生长优势和再生刺激是供体肝细胞增殖所必需的。当前的研究工作集中在供体肝细胞响应肝损伤/预处理而扩增的机制上。此外,最新临床证据表明,HT的重要障碍包括优化植入和有限的有效持续时间,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法,以及跟踪细胞移植功能和接近临床的细胞来源的新方式。

总结

HT在有限时间内部分纠正了遗传疾病,并与急性肝衰竭的逆转有关。使HT成为一种治愈方法仍存在的主要障碍包括提高植入率,以及监测细胞移植功能和排斥反应的方法。本综述旨在讨论临床HT的当前技术水平,并深入探讨为克服这些障碍而采取的创新方法。

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