干细胞研究或迎来“黄金时代”

 2012年06月20日07:46 来源：科学时报 作者：赵路 本报讯（记者赵路）10多年来，干细胞疗法一直被认为能够给那些遭受遗传和退行性疾病折磨的人带来希望。而就在几天前，随着两个研究团队在于日本横滨召开的国际干细胞研究学会（ISSCR）年会上宣告了他们在人类临床研究中取得的成果一项聚焦于罕见的遗传神经病，另一项则着眼于老年人的视力丧失，这一希望又朝着现实迈出了一步。 美国加利福尼亚州纽瓦克市干细胞公司报告了用人体神经干细胞治疗梅氏病（PMD）所取得的鼓舞人心的研究成果。PMD是一种渐进式的致命疾病，该病通过基因突变抑制了髓鞘的正常生长，后者是大脑中包裹神经纤维的一种保护物质。缺乏髓鞘，神经信号便会流失；病人，通常是婴儿，便会经历运动协调能力退化以及其他神经病症状。据干细胞公司负责研究的副总裁Ann Tsukamoto介绍，该公司之所以选择PMD来测试其神经干细胞技术，缘于目前尚没有这种疾病的治疗方法，且通过基因检测和磁共振成像能够确诊这种疾病。她说："这便为最有效的早期介入创造了一个机会。" 该公司建立了一个从成熟神经组织中分离出的高度纯化的神经干细胞库。研究人员将这些神经干细胞注入啮齿动物体内后，它们并没有形成肿瘤，事实上，这些细胞在小鼠的大脑中游走，并分化成不同类型的神经细胞，其中就包括分泌能够保护神经纤维的髓鞘的细胞。Tsukamoto介绍说，当神经干细胞被注入小鼠后，它们表现出了"强大的移植和迁移能力，并形成新的髓鞘"。 该公司如今正赞助对4名PMD婴幼儿患者进行该技术的初期安全试验。加利福尼亚大学旧金山分校的研究人员，向每位患者大脑中的4个区域中的每一个区域移植了7500万个神经干细胞，并随之进行了免疫抑制治疗，这样受体才不会排斥外来的细胞。Tsukamoto报告说，在试验过程中并没有出现安全隐患。此外，在18个月后进行的磁共振成像显示，在轴突周围形成了新的髓鞘，并且对患者进行的临床观察表明，他们的运动机能保持稳定或出现了小幅提升。干细胞公司如今正计划进行更大规模的试验。Tsukamoto表示，一旦这种疗法被证明是有效的，它将带来多发性硬化、大脑性麻痹和阿尔茨海默氏症的神经干细胞新疗法。 在这次会议上，神户市日本理化研究所（RIKEN）发育生物学中心的干细胞研究人员Masayo Takahashi，报告了她的研究小组在针对与年龄相关的黄斑变性（AMD）的临床前研究所取得的进展。在AMD中，视网膜色素上皮（RPE）细胞的生长出现了问题，并且位于视网膜下部的血管出现了渗漏。这些情况导致眼睛中心部位的视力下降。Takahashi的研究小组研制出一种方法，即用外科手术摘除有问题的血管，同时用源自病人自身细胞的新RPE细胞替代受损的RPE细胞。利用被称为细胞再编程的一项技术，研究人员采集了病人的皮肤细胞，并将其转化为所谓的诱导多能干（iPS）细胞，这种细胞能够分化成人体中的所有细胞。研究人员随后将iPS细胞转化为RPE细胞。由于iPS方法使用的是病人自身的细胞，因此避免了对免疫抑制药物的需求。 由Takahashi小组生成的RPE细胞表现出了真正人体RPE细胞的特征结构和基因表达模式。她报告说，将它们注入小鼠并没有引发肿瘤，并且这些细胞在移植到猴子体内后存活了6个多月。Takahashi希望在得到必要的批准后，能够在1年内开展人体试验。 英国剑桥研究学院癌症中心的干细胞研究人员Fiona Watt指出，在ISSCR上发表的这些研究结果将帮助该领域"积攒力量"。而美国哈佛医学院的干细胞科学家George Daley则更为乐观。他说，记住这次年会上报告的这些进展；并表示对明年在波士顿召开的2013年ISSCR年会充满期待。

Stem Cells Move Into Prime Time

by Dennis Normile on 18 June 2012, 2:50 PM   Ring of protection. In experiments, myelin produced by injected human neural stem cells (inset, green) formed protective sleeves around the nerve fibers in mouse brains (red). A separate group can derive retinal pigment epithelial cells from a patient's own skin cells (in dish) to treat age-related macular degeneration. Credit: RIKEN CDB; StemCells Inc. YOKOHAMA, JAPAN—For more than a decade, stem cell therapies have been touted as offering hope for those suffering from genetic and degenerative diseases. The promise took another step toward reality last week with announcements here at the annual meeting of the International Society for Stem Cell Research (ISSCR) that two groups are moving forward with human clinical research, one focusing on a rare genetic neurological disease and the other for the loss of vision in the elderly. StemCells Inc. of Newark, California, reported encouraging results of an initial human trial using human neural stem cells to treat Pelizaeus-Merzbacher disease (PMD). PMD is a progressive and fatal disorder in which a genetic mutation inhibits the normal growth of myelin, a protective material that envelopes nerve fibers in the brain. Without myelin, nerve signals are lost, and the patient, usually an infant, suffers degenerating motor coordination and other neurological symptoms. In her presentation, Ann Tsukamoto, StemCells' vice president for research, said the company chose to test its neural stem cell approach on PMD because there is currently no treatment for the condition and a diagnosis can be confirmed by genetic testing and magnetic resonance imaging. "This creates an opportunity for early intervention when it can best help." The company has created banks of highly purified neural stem cells that are isolated from adult neural tissue. Injected into rodents, the cells don't form tumors; rather, they migrate through the animals' brains, where they differentiate into various types of neural cells including the cells that create the myelin that protects nerve fibers. When neural stem stems were injected into in mice, they showed "robust engraftment and migration, the formation of new myelin," Tsukamoto said. The company has now sponsored an initial safety trial of the strategy in four infants with PMD. In each patient, researchers at University of California, San Francisco, transplanted 75 million neural stem cells into each of four sites in the brain and followed that with immunosuppressive therapy so the recipient wouldn't reject the foreign cells. No safety concerns arose during the trial, Tsukamoto reported. Moreover, magnetic resonance imaging taken 18 months later indicated the formation of new myelin around axons and clinical observations of the treated patients indicated that their motor functions remained stable or enjoyed modest gains. The company is now planning larger trials. Tsukamoto says that if the therapy proves efficacious it could lead to neural stem cell treatments for multiple sclerosis, cerebral palsy, and Alzheimer's disease. In a second talk at the meeting, stem cell researcher Masayo Takahashi of the RIKEN Center for Developmental Biology in Kobe reported on progress in her group's preclinical work targeting wet-type age-related macular degeneration (AMD). In AMD, the retinal pigment epithelial (RPE) cells that support the cells in the eye that detect light wear out, and there is also the growth of abnormal, leaky blood vessels below the retina. These conditions lead to impaired vision in the central part of the eye. Her group's proposed strategy is to surgically remove the problematic blood vessels and replace the damaged RPE cells with new RPE cells derived from a patient's own cells. Using a process called cellular reprogramming, the researchers take a patient's skin cells, convert them into so-called induced pluripotent stem (iPS) cells, which can differentiate into all the cells within the human body. They then transform those iPS cells into RPE cells and form them into sheets in the lab. Since the iPS approach uses the patient's own cells, they avoid the need for immunosuppressive drugs. The RPE cells generated by Takahashi's team show the characteristic structure and gene expression pattern of authentic human RPE cells. Injections of the cells into mice triggered no tumors, she also reported, and the cells survived for more than 6 months when transplanted into monkeys. The research team has not directly tested whether the transplanted RPE cells improved the animal's vision. But Takahashi notes that some people with AMD have had RPE cells transplanted from the periphery to the center of their eyes, improving their central vision. She hopes to have all necessary approvals for research with human subjects within a year. Earlier this year, scientists at University of California, Los Angeles, and Advanced Cell Technology of Marlborough, Massachusetts, reported in The Lancet about the safe and successful use of RPE cells derived from human embryonic stem cells, rather than iPS cells, to treat a different type of AMD in a limited number of human patients. Takahashi predicts that in the future, selecting from different stem cell therapies will "depend on the target disease and the situation of the host." The positive results reported in The Lancet paper and presented at ISSCR will help the field "gather momentum," says Fiona Watt, a stem cell researcher the Cancer Research UK Cambridge Research Institute. And George Daley, a stem cell scientist at Harvard Medical School in Boston, is even more upbeat. Noting the progress reported at this year's conference, he says, "Wait until next year in Boston," the site of the 2013 ISSCR meeting.