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用于肝脏再生的干细胞和祖细胞:我们能否将从实验室到临床的过程标准化?

Stem and progenitor cells for liver repopulation: can we standardise the process from bench to bedside?

作者信息

Sancho-Bru P, Najimi M, Caruso M, Pauwelyn K, Cantz T, Forbes S, Roskams T, Ott M, Gehling U, Sokal E, Verfaillie C M, Muraca M

机构信息

Stem Cell Institute, Katholieke Universiteit Leuven, Belgium.

出版信息

Gut. 2009 Apr;58(4):594-603. doi: 10.1136/gut.2008.171116. Epub 2008 Dec 17.

Abstract

There has been recent progress in the isolation and characterisation of stem/progenitor cells that may differentiate towards the hepatic lineage. This has raised expectations that therapy of genetic or acquired liver disease might be possible by transplanting stem/progenitor cells or their liver-committed progeny. However, it is currently impossible to determine from the many documented studies which of the stem/progenitor cell populations are the best for therapy of a given disease. This is largely because of the great variability in methods used to characterise cells and their differentiation ability, variability in transplantation models and inconsistent methods to determine the effect of cell grafting in vivo. This manuscript represents a first proposal, created by a group of investigators ranging from basic biologists to clinical hepatologists. It aims to define standardised methods to assess stem/progenitor cells or their hepatic lineage-committed progeny that could be used for cell therapy in liver disease. Furthermore standardisation is suggested both for preclinical animal models to evaluate the ability of such cells to repopulate the liver functionally, and for the ongoing clinical trials using mature hepatocytes. Only when these measures have been put in place will the promise of stem/progenitor-derived hepatocyte-based therapies become reality.

摘要

最近在分离和鉴定可能向肝系分化的干细胞/祖细胞方面取得了进展。这引发了人们的期望,即通过移植干细胞/祖细胞或其肝定向子代来治疗遗传性或获得性肝病或许是可行的。然而,从众多已发表的研究中目前尚无法确定哪些干细胞/祖细胞群体最适合治疗特定疾病。这主要是因为用于鉴定细胞及其分化能力的方法差异很大,移植模型存在差异,以及确定细胞移植在体内效果的方法不一致。本手稿是由一组从基础生物学家到临床肝病学家的研究人员提出的首个提议。其目的是定义标准化方法,以评估可用于肝病细胞治疗的干细胞/祖细胞或其肝系定向子代。此外,建议对评估此类细胞在功能上使肝脏再生能力的临床前动物模型以及正在进行的使用成熟肝细胞的临床试验都进行标准化。只有当这些措施落实到位后,基于干细胞/祖细胞的肝细胞疗法的前景才会成为现实。

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