[英语，新闻]Induction of functional hepatocyte-like cells from mouse fibrob

StephenW

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10116.html#/affil-auth
Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factorsAffiliations         

• Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy for Sciences, Yueyang Road 320, 200031 Shanghai, China :Zhiying He, Shuyi Ji, Huawang Sun, Changcheng Liu,Xin Wang &Lijian Hui
• Department of Cell Biology, Second Military Medical University, 800 Xiangyin Road, 200433 Shanghai, China: Zhiying He,Dao Xiang,Changcheng Liu &Yiping Hu
• University of Minnesota, Minneapolis: Xin Wang
•                                        
  Stem Cell Institute, University of Minnesota, Minneapolis, 55455 Minnesota, USA :                 Xin Wang
  

        
Contributions   L.H. conceived the project. P.H. performed most of the experiments. S.J. analysed the in vitro functions of iHep cells. H.S. analysed gene expression of iHep cells. L.H., X.W., P.H. and Z.H. designed the experiments for characterizing in vivo functions of iHep cells. P.H., Z.H., D.X., C.L. and Y.H. performed the in vivo experiments. L.H. and P.H. analysed the data. L.H., P.H. and X.W. wrote the manuscript.
        

The generation of functional hepatocytes independent of donor liver organs is of great therapeutic interest with regard to regenerative medicine and possible cures for liver disease1. Induced hepatic differentiation has been achieved previously using embryonic stem cells or induced pluripotent stem cells2, 3, 4, 5, 6, 7, 8. Particularly, hepatocytes generated from a patient’s own induced pluripotent stem cells could theoretically avoid immunological rejection. However, the induction of hepatocytes from induced pluripotent stem cells is a complicated process that would probably be replaced with the arrival of improved technology. Overexpression of lineage-specific transcription factors directly converts terminally differentiated cells into some other lineages9, 10, 11, 12, including neurons13, cardiomyocytes14 and blood progenitors15; however, it remains unclear whether these lineage-converted cells could repair damaged tissues in vivo. Here we demonstrate the direct induction of functional hepatocyte-like (iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4, Hnf1α and Foxa3, and inactivation of p19Arf. iHep cells show typical epithelial morphology, express hepatic genes and acquire hepatocyte functions. Notably, transplanted iHep cells repopulate the livers of fumarylacetoacetate-hydrolase-deficient (Fah−/−) mice and rescue almost half of recipients from death by restoring liver functions. Our study provides a novel strategy to generate functional hepatocyte-like cells for the purpose of liver engineering and regenerative medicine.



(6.合.彩).足球.篮球...各类投注开户下注

第一投注.现金网:招代理年薪10万以上:6668.cc

StephenW

对供肝肝细胞生成器官独立的功能是非常有关再生医学和治疗肝disease1可能治愈的兴趣。分化诱导肝已经取得了以前使用的胚胎干细胞或诱导多能干cells2，3，4，5，6，7，8。特别是，肝细胞产生患者自身的诱导多能干细胞，理论上避免免疫排斥反应。然而，从肝细胞诱导多能干细胞诱导是一个复杂的过程，很可能会与改进技术的到来取代。宗族特有的转录因子过度终末分化细胞直接转换成其他lineages9，10，11，12，包括neurons13，cardiomyocytes14和血液progenitors15，但目前还不清楚是否这些谱系细胞能修复受损的转换在体内组织。在这里，我们证明了肝细胞的功能类似通过Gata4，Hnf1α和Foxa3转导小鼠尾巴尖成纤维细胞（高能物理）细胞，并直接诱导因子p19ARF失活。中国科学院高能物理上皮细胞呈现典型的形态，表达的基因，获得肝肝细胞的功能。值得注意的是，高能所移植的细胞重新填充fumarylacetoacetate-水解酶缺陷（华氏- /- ）小鼠的肝脏和救援从死亡恢复肝功能，几乎一半的收件人。我们的研究提供了一种新的策略，产生功能性肝细胞样的肝脏工程和再生医学的目的细胞。

StephenW

Scientists generate liver cells from skin

By David Mark

Posted Thu May 12, 2011 12:53pm AEST

A team of scientists in China has found a way to restore damaged livers using adult skin stem cells.

The technique raises the possibility of what one liver specialist is calling the "Holy Grail" - that people now needing liver transplants could be simply treated with an injection of their own cells.
Researchers spent three years on the study in which they took skin cells from mice to reproduce fully functional liver cells.
The results, being published in the Journal of Nature today, show the mice were able to live healthy lives.
Professor Geoff McCaughan, the head of the Liver Research Program at the Centenary Research Institute at the University of Sydney, is excited by the Chinese team's work.
He has worked nationally and internationally in the field of liver transplants for 25 years and says the findings could have dramatic ramifications.
Every year, around 200 Australians have a liver transplant.
"The commonest cause for liver transplantation is the adult community in the western world is people with chronic hepatitis C infection who develop sclerosis or liver cancer," Professor McCaughan said.
The Chinese scientists have generated large amounts of liver cells in the test tube.
"Then using them to treat animals, in this case a mouse, then dying of liver failure with 100 per cent mortality or 100 per cent death rate, and then transfusing these new cells and only having a 50 per cent death rate," he said.
"The really exciting bit is that they've generated these liver cells from non-liver cells - what they've done is get them out of old skin and then transform these cells from skin cells into liver cells."
Professor McCaughan says the process should be achievable with human cells.
But he says people would have to also stop whatever was producing the liver damage in the first place.
"You would have to have drugs and other treatments to control the toxicity while the new cells in a human grow and weren't subjected to the same toxicities," he said.
"So that's an important concept and an important difference between doing it in humans and doing it in mice.
"Conceptually, it could be done, there's no question about that."
Professor McCaughan says the technique, if it worked for humans, would first be used to keep people alive while they waited for a transplant.
"If that worked and that was successful, then people could undertake the Holy Grail with this type of approach," he said.
"On an individual basis, which would be enormously resource intensive, you would essentially be having to have a group of scientists and medical people working on an individual patient's cells in the test tube in a laboratory in the same for liver disease in the same way they do now for bone marrow transplantations.
"But that would be the Holy Grail ... that's the dream, we love to live the dream."