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临床肝细胞移植:实际限制与可能的解决方案。

Clinical hepatocyte transplantation: practical limits and possible solutions.

作者信息

Gramignoli Roberto, Vosough Massoud, Kannisto Kristina, Srinivasan Raghuraman C, Strom Stephen C

机构信息

Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

出版信息

Eur Surg Res. 2015;54(3-4):162-77. doi: 10.1159/000369552. Epub 2015 Jan 23.

DOI:10.1159/000369552
PMID:25633583
Abstract

Since the first human hepatocyte transplants (HTx) in 1992, clinical studies have clearly established proof of principle for this therapy as a treatment for patients with acquired or inherited liver disease. Although major accomplishments have been made, there are still some specific limitations to this technology, which, if overcome, could greatly enhance the efficacy and implementation of this therapy. Here, we describe what in our view are the most significant obstacles to the clinical application of HTx and review the solutions currently proposed. The obstacles of significance include the limited number and quality of liver tissues as a cell source, the lack of clinical grade reagents, quality control evaluation of hepatocytes prior to transplantation, hypothermic storage of cells prior to transplantation, preconditioning treatments to enhance engraftment and proliferation of donor cells, tracking or monitoring cells after transplantation, and the optimal immunosuppression protocols for transplant recipients.

摘要

自1992年首次进行人类肝细胞移植(HTx)以来,临床研究已明确证实了这种疗法作为治疗获得性或遗传性肝病患者的原理。尽管已取得了重大成就,但该技术仍存在一些特定限制,若能克服这些限制,可极大提高该疗法的疗效和应用。在此,我们阐述我们认为HTx临床应用中最显著的障碍,并综述目前提出的解决方案。重要障碍包括作为细胞来源的肝组织数量有限和质量欠佳、缺乏临床级试剂、移植前肝细胞的质量控制评估、移植前细胞的低温保存、增强供体细胞植入和增殖的预处理、移植后细胞的追踪或监测,以及移植受者的最佳免疫抑制方案。

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