[號外]英國成功培植肝臟細胞 - 肝胆相照论坛

Liver Cells Grown From Patients’ Skin Cells
Could Lead to Treatment of Liver Diseases

http://www.mcw.edu/Releases/2009 ... lsfromSkinCells.htm

Oct 9 - Scientists at The Medical College of Wisconsin in Milwaukee have successfully produced liver cells from patients’ skin cells opening the possibility of treating a wide range of diseases that affect liver function. The study was led by Stephen A. Duncan, D.Phil, Marcus Professor in Human and Molecular Genetics, and professor of cell biology, neurobiology and anatomy, along with postdoctoral fellow Karim Si-Tayeb, PhD, and graduate student Ms. Fallon Noto.

“This is a crucial step forward towards developing therapies that can potentially replace the need for scarce liver transplants, currently the only treatment for most advanced liver disease,” says Dr. Duncan.

Liver disease is the fourth leading cause of death among middle aged adults in the United States. Loss of liver function can be caused by several factors, including genetic mutations, infections with hepatitis viruses, by excessive alcohol consumption, or chronic use of some prescription drugs. When liver function goes awry it can result in a wide variety of disorders including diabetes and atherosclerosis and in many cases is fatal.

The Medical College research team generated patient–specific liver cells by first repeating the work of James Thomson and colleagues at University of Wisconsin-Madison who showed that skin cells can be reprogrammed to become cells that resemble embryonic stem cells. They then tricked the skin–derived pluripotent stem cells into forming liver cells by mimicking the normal processes through which liver cells are made during embryonic development. Pluripotent stem cells are so named because of their capacity to develop into any one of the more than 200 cell types in the human body.

At the end of this process, the researchers found that they were able to very easily produce large numbers of relatively pure liver cells in laboratory culture dishes. “We were excited to discover that the liver cells produced from human skin cells were able to perform many of the activities associated with healthy adult liver function and that the cells could be injected into mouse livers where they integrated and were capable of making human liver proteins,” says Dr. Duncan.

Several studies have shown that liver cells generated from embryonic stem cells could potentially be used for therapy. However, the possible use of such cells is limited by ethical considerations associated with the generation of embryonic stem cells from preimplantation embryos and the fact that embryonic stem cells do not have the same genetic make-up as the patient.

Although the investigations are still at an early stage the researchers believe that the reprogrammed skin cells could be used to investigate and potentially treat metabolic liver disease. The liver may be particularly suitable for stem-cell based therapies because it has a remarkable capacity to regenerate. It is interesting to note that the regenerative nature of the liver was referenced in the ancient Greek tale of Prometheus. When Prometheus was caught stealing the gift of fire from Zeus, he was punished by having his liver eaten daily by an eagle. This provided the eagle with an everlasting meal because each night the liver of Prometheus would re-grow.

The liver is a central regulator of the body’s metabolism and is responsible for controlling sugar and cholesterol levels, secretion of a variety of hormones, production of blood clotting factors, and has an essential role in preventing toxins from damaging other organs in the body.
It is possible that in the future a small piece of skin from a patient with loss of liver function could be used to produce healthy liver cells, replacing the diseased liver with normal tissue.

Recently, the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases through the American Recovery and Reinvestment Act have provided Medical College researchers, in collaboration with Markus Grompe, MD, at the Oregon Health and Science University, a $1 million research grant to pursue the possibility of using reprogrammed skin cells to study and treat metabolic liver disease. Using this support, as well as donations from individuals throughout Milwaukee, Medical College researchers are currently producing reprogrammed cells from patients suffering from diabetes, hyperlipidemia, and hypercholesterolemia in an effort to identify new treatments for these diseases.

人民日报：干细胞研究的突破

张树庸　赵贵英《人民日报》( 2009年1月30日 03 版)

　　干细胞研究是国际生物学界的一个热点，2008年因为成果卓著而被美国著名《科学》杂志列为当年十大科学突破榜首。

　　科学家将病人自身的皮肤细胞进行基因重组，使皮肤细胞重新编程逆转成人胚胎干细胞，这一技术成果有望为人类最终治愈帕金森氏症和老年痴呆症等顽症带来希望。

　　早在1978年11月，美国威斯康星州的科学家宣布他们培育出了人体胚胎干细胞，但是，因为提取干细胞进行研究会毁坏胚胎，这项研究引发了生物伦理学的激烈争论，以美国为首的很多国家都颁布了禁令，限制科学家对人体胚胎干细胞的研究。

　　2006年，日本京都大学的教授发现了避开生物伦理学困境研究人体干细胞的途径。次年11月，日、美科学家同时宣布，利用基因转移技术，向皮肤细胞中注入4个基因，可成功地将人体皮肤细胞改造成几乎和胚胎干细胞完全相似的干细胞。这一成果可以避开利用晶胚或卵母细胞获得的胚胎干细胞的伦理争议，因为这些皮肤细胞都是取源于患者的自体细胞，不会产生排异现象。

　　2007年11月21日，美国《科学》和《细胞》杂志同时发表论文宣告人类首次经非克隆技术培育出人体胚胎干细胞，这一成果轰动了全世界，为干细胞研究在医学领域的广泛应用开辟了新的道路。在此基础上，近一年科学家们在细胞基因重组获得“量身定制”细胞系研究上和提取胚胎干细胞方面获得重大突破。

　　科学家多年来梦想在患者身上提取细胞制造出能长期生存的细胞系。因为大多数成熟细胞在培养皿中不能成活，所以直接从患者身上提出用于研究的细胞是不能实现的。2008年梦想成真，一个研究组为10种疾病的患者培育成功多能干细胞(ips细胞)，其中包括肌肉萎缩症、青少年糖尿病、唐氏综合征、帕金森氏症、亨廷顿舞蹈病等。这10种疾病很难甚至不能用动物模型进行研究，而用基因重组再编程的细胞可为科学家研究疾病分子基础提供工具。这些细胞或许还将对候选药物的筛选有所帮助。最终，这种方法可让科学家在培养皿中修正基因缺陷，然后用修复了的自身细胞为患者治疗疾病。

　　尤其令人兴奋的是，干细胞的研究成果已开始用于治疗。由英国、意大利、西班牙三国科学家组成的研究小组，利用部分由成人干细胞培养的气管，成功地给一位30岁的西班牙患者进行气管移植。该成果发表在2008年11月19日的《柳叶刀》杂志上。据悉，手术后12天女患者出院能过正常生活，并能参加跳舞活动。经过数次血液检查后，未发现体内有免疫排斥信号。

　　科学家们表示，这次手术的成功是干细胞技术的重大突破，不久的将来，用干细胞培植的器官移植术就可发展成常规手术。将来，心、肝、肺等器官的培植和移植就会像机器零件的生产和更换一样方便。

http://tech.sina.com.cn/d/2009-01-30/09592780588.shtml