利用患者皮肤细胞创建肝细胞 - 丁香园论坛

Liver Cells Created from Patients' Skin Cells
利用患者皮肤细胞创建肝细胞
译者：Docofsoul
ScienceDaily (Aug. 28, 2010) — By creating diseased liver cells from a small sample of human skin, scientists have now shown that stem cells can be used to model a diverse range of inherited disorders. The University of Cambridge researchers' findings, which will hopefully lead to new treatments for those suffering from liver diseases, were published August 25 in The Journal of Clinical Investigation.
《每日科学》2010年8月28日报道 —— 利用小样本人类皮肤构建病理性肝细胞，科学家们目前已经显示：干细胞可为多种多样的遗传性疾病建模。剑桥大学研究者们的这项发现有希望为肝病患者提供新的疗法。该研究结果发表于8月25号的《临床研究杂志》（The Journal of Clinical Investigation）。

Diseased liver cells. (Credit: Dr Tamir Rashid.)
病理性肝细胞（照片来源：Tamir Rashid博士）
Because liver cells (hepatocytes) cannot be grown in the laboratory, researching liver disorders is extremely difficult. However, today's new research, which was funded by the Wellcome Trust and the Medical Research Council (MRC), demonstrates how to create diseased liver-like cells from patients suffering from a variety of liver disorders.
因为肝细胞无法在实验室中培养，所以研究肝病特别困难。不过，今天的新的研究则显示了利用各种肝病患者自身组织来创建病理性肝样细胞的具体方法。本研究由英国卫尔康信托与英国医学研究委员会（MRC）提供研究资金。
By replicating the organ's cells, researchers can not only investigate exactly what is happening in a diseased cell, they can also test the effectiveness of new therapies to treat these conditions. It is hoped that their discovery will lead to tailored treatments for specific individuals and eventually cell-based therapy -- when cells from patients with genetic diseases are 'cured' and transplanted back. Additionally, as the process could be used to model cells from other parts of the body, their findings could have implications for conditions affecting other organs.
通过复制该器官的细胞，研究者不仅能够精确审查正在患病的细胞内所发生的情形，还能够测试治疗这些疾病的新疗法的效力。他们的发现有望为特定患者提供个体化治疗；并且，当来自遗传病患者的细胞被“治愈”而且被重新移植到患者本身，实际上就意味着医生提供了基于细胞的（特效）疗法。此外，由于这一过程可用于定制来自身体其它部分的细胞， 因此本发现可能对影响其它器官的疾病也有意义。
Dr Ludovic Vallier of the MRC Centre for Stem Cell Biology and Regenerative Medicine, University of Cambridge, principal investigator of the research, said: "Our work represents an important step towards delivering the clinical promises of stem cells. However, more work remains to be done and our group is dedicated to achieving this ultimate goal by increasing the knowledge necessary for the development of new therapies."
剑桥大学干细胞生物学与再生医学MRC中心、本研究的首席研究员Ludovic Vallier博士说：“我们的工作代表着向干细胞实现临床应用方向迈出的重要一步。不过，更多的工作还需要完成。我们的团队正致力于通过丰富开发新疗法所必需的知识来达成这一终极目标。”
In the UK, liver disease is the fifth largest cause of death after cardiovascular, cancer, stroke, and respiratory diseases. Over the past 30 years mortality from liver disease in young and middle-aged people has increased over six times, with the number of individuals dying from the disease increasing at a rate of 8-10 per cent every year.
在英国，肝病是继心血管、癌症、中风与呼吸疾病之后的第五大死因。在过去的30年里，中青年的肝病死亡率提高了六倍，每年死于肝病的人数以8-10%的速率递增。
By 2012, the UK is expected to have the highest liver disease death rates in Europe and, without action to tackle the disease, it could overtake stroke and coronary heart disease as the leading cause of death within the next 10-20 years. In the United States, it accounts for approximately 25,000 deaths a year.
到2012年，英国预期肝病死亡率将高居欧洲首位。如果不采取相应措施，则在未来的20-30年，将超过中风与冠心病，成为第一大死亡原因。在美国，肝病每年夺去大约二万五千人的生命。
For their research, the scientists took skin biopsies from seven patients who suffered from a variety of inherited liver diseases and three healthy individuals (the control group). They then reprogrammed cells from the skin samples back into stem cells.
为了研究，科学家们从几位患者（实验组，各患有不同的遗传性肝病）以及三个健康人（作为对照组）身上提取了皮肤活检组织，然后重新调整使皮肤样本细胞返回干细胞状态。
These stem cells were then used to generate liver cells which mimicked a broad range of liver diseases -- the first time patient-specific liver diseases have been modelled using stem cells -- and to create 'healthy' liver cells from the control group. Importantly, the three diseases the scientists modelled covered a diverse range of pathological mechanisms, thereby demonstrating the potential application of their research on a wide variety of disorders.
然后用这些干细胞产生模拟范围广泛的各种肝病的肝细胞 —— 利用干细胞来给特定患者的肝病建立模型在历史上尚属首次 —— 同时也用来自对照组的干细胞建立“健康”肝细胞。重要的是，科学家用于建模的三种疾病涵盖了多种多样的病理范围，从而显示了其研究结果可用于一个很大范围内的各种疾病的潜力。
Dr Tamir Rashid of the Laboratory for Regenerative Medicine, University of Cambridge, lead author of the paper, said: "We know that given the shortage of donor liver organs alternative strategies must urgently be sought. Our study improves the possibility that such alternatives will be found -- either using new drugs or a cell-based therapeutic approach."
论文的第一作者、剑桥大学再生医学实验室的Tamir Rashid博士说：“众所周知，因为捐赠的肝器官数量严重不足，必须紧急寻求各种替代方案。我们的研究改善了替代方案被发现的可能性 —— 可用新药，或用细胞学疗法。”
Professor Mark Thursz, a specialist in liver disease and Professor of Hepatology at Imperial College (who was not affiliated with the study), commented on the importance of the research: "Liver disease is the fifth most common cause of mortality in many developed countries and unlike the other leading causes of death, the rate of liver related mortality is increasing.
"The development of patient specific liver cell lines from stem cells is a significant advance in the battle against liver diseases. This technology holds promise in the short term by providing new tools to explore the biology of liver diseases and in the long term as a potential source of liver cells for patients with liver failure."
Mark Thursz教授是肝病专家、帝国理工学院肝病学教授（未参与本研究），就该研究的重要性进行了评论：“肝病是许多发达国家的第五大死亡原因，并且，与其它主要死亡原因不同，肝相关死亡率在日益增加。对患者特定的肝细胞系的开发是战胜肝病的斗争中的一次重大进步。该技术通过提供探索肝病生物学的新工具，从短期角度来看将有所作为，而从长期角度来看，则为肝衰病人提供了肝细胞潜力源。”
（Docofsoul 译于2010-08-30）