中国科学家称,他们已通过将人类皮肤细胞与兔子卵细胞融合的方法培植出了人类胚胎干细胞,开创了克隆研究方面的一个先河。
中国的学术期刊《细胞研究》(Cell Research)网络版周三刊载了此项研究的成果。然而,美国科学家却对此产生了质疑。此类研究在美国仍存在争议。
据知情的研究人员称,包括《科学》(Science)及《美国国家科学院院刊》(Proceedings of the National Academy of Sciences)在内的西方顶级期刊对中国科学家的此项研究进行评审之后,均拒绝进行刊载。
此项研究是在曾于美国留学的上海第二医科大学(Shanghai Second Medical University)沈慧真(HuiZhen Sheng)博士的领导下展开的。尽管他们的研究成果刚刚被刊载出来,但学术界对该项研究的争论已长达一年半以上。
如果成果属实,这将是人类首次通过克隆培植出人类胚胎干细胞。有人提议将这种被称为治疗性克隆的方法用来培育与病人完全相匹配的神经或其他组织。
美国学术界对治疗性克隆的研究仅获得了有限的成果。在2001年11月,一家名为Advanced Cell Technology Inc.的小型生物科技公司表示,该公司利用从女性志愿者身上采集的卵细胞培植出了早期胚胎,但未能得到干细胞。
在美国,进行克隆人类胚胎的研究会遭遇多重阻碍,如在伦理道德方面、以及人类卵细胞的采集方面。
中国的研究人员在实验中则选用了较为容易获得的兔子卵细胞。研究人员先将兔子卵细胞中的DNA去除,然后将人类皮肤细胞植入其中。这些经过处理的卵细胞随后发育成含有人类基因物质的胚胎。数天之后,研究人员将这些卵细胞解剖,从中提取出干细胞。
一位曾对刊载在《细胞研究》上的此项研究成果进行过评审的美国科学家表示,研究人员未能证明所获得的便是真正的胚胎干细胞,而且也未能满足学术界要求其提供更多数据这一非常合理的要求。
记者未能联系到沈慧真博士,请其对这位美国科学家的讲话发表评论。
但熟悉此项研究的德州大学西南医学中心(University of Texas Southwestern Medical Cente)研究人员David Garbers指出,如果沈慧真博士的工作得到验证,这将是医学界一个非常了不起的进步。医生以后可以不用借助人类卵细胞便可从患者身上提取出胚胎干细胞,之后利用变异的方法把它们培育成一个可供人类移植的细胞。
Chinese fusion method promises fresh route to human stem cells
CARINA DENNIS
Biologists in China have reprogrammed human cells by fusing them with rabbit eggs emptied of their genetic material. And they have extracted stem cells, which have the potential to form a wide array of different cell types, from the resulting embryos.
C. DENNIS; SHANGHAI SECOND MEDICAL UNIV.
A team led by Huizhen Sheng (left) has devised a technique for reprogramming adult human cells by fusing them with empty rabbit eggs (above).
The researchers, led by Huizhen Sheng of Shanghai Second Medical University, think that these 'derived' stem cells could provide scientists in the field with an alternative to stem-cell lines extracted from human embryos. But some researchers who have seen the work point out that the derived cells don't seem to have the same ability as human embryonic stem cells to grow indefinitely in culture.
The work will be published online this week in Cell Research, a peer-reviewed journal supported by the Chinese Academy of Sciences. The paper will appear in print later this month (Y. Chen et al. Cell Res. 13, 251–263; 2003).
Sheng's work has already created a buzz after rumours of it circulated in the scientific community and were reported in The Wall Street Journal in March 2002 (see Nature 419, 334–336; 2002). The publication is likely to reignite debate over the ethics of cross-species reprogramming. But cell biologists say that having the data available for public discussion will help researchers and regulators to decide what kinds of cross-species work should be pursued.
Reprogramming adult cells to assume an embryonic state could offer a way to grow new cells and tissues to replace those lost to ageing and disease. And using an individual's own cells, in a process often called therapeutic cloning, may avoid problems of the immune system rejecting the cell therapy.
To reprogramme an adult cell, it can either be fused with or have its nucleus injected into an egg that has had its own nucleus removed. The reconstituted cell is then tricked into dividing as if it were an embryo, with all memory of its previous life as a liver, skin or kidney cell erased. After 5–7 days, embryonic stem cells — which can seemingly grow indefinitely — can be extracted from the growing ball of cells. By changing the growth conditions, these cells can then be coaxed to develop into many different cell types.
Until now, scientists have only been able to generate animal stem-cell lines from the reprogrammed nuclei of cells. "This is the first paper to convincingly show that you can get human reprogramming," says Robin Lovell-Badge, a cell biologist at the National Institute for Medical Research in London.
Sheng claims to have successfully reprogrammed cells from the foreskin tissues of males aged 5, 42 and 52 years and from the facial skin of a 60-year old woman. "It just goes to show that age doesn't matter," says Lovell-Badge.
But Sheng has had a tough time convincing some experts. "I first submitted the paper more than two years ago," she says. It is understood that the paper was considered and rejected by other journals before this week's publication in China.
"I was frustrated that it took so long to get the paper published," Sheng says, "and it still may take a while for people to accept the work. But the scientific community has the right to question the details of the work and we have a responsibility to respond to them."
Doug Melton a cell biologist at Harvard University, for one, has concerns about the nature of the derived embryonic stem-cell lines. "I'm convinced that the cells do have the capacity to differentiate into different cell types, but it's unclear how long the cells can grow in culture," he says.
"It would be very surprising if the cell lines were stable," Melton adds, noting that many interspecies hybrids are unstable, because of incompatibilities between the nucleus and mitochondria (the energy-producing compartments of cells) from different species.
And Rudolf Jaenisch, of the Whitehead Institute in Cambridge, Massachusetts, is not convinced that the derived cells meet the usual criteria for embryonic stem cells. "An important criterion is indefinite growth," he says. "This is not shown."
But reservations aside, Melton is pleased that the work has finally seen the light of day. "I'm glad to see it published as it will encourage others to try it," he says.
At this stage, Sheng has no plans to use stem cells created by her method to treat humans. "It is a research tool. But there is the possibility that if it were proved to be safe enough for clinical use, it could provide a solution to human egg shortages for reprogramming in the future," says Sheng.
While the scientific community debates her work, Sheng is keen to test the embryonic stem cells she has generated in an animal model. "It will be important to see whether they will be tolerated by the immune system and whether they can correct an animal model of human disease," she says.
Nature 424, 711 (14 August 2003); doi:10.1038/424711a