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Blastomere Blowup

A novel way to harvest stem cells intrigues and inflames
OUTRAGE, AGAIN:



David Scharf Photo Researchers, Inc.
A method that can generate human embryonic stem cells without harming embryos? In August biotechnology firm Advanced Cell Technology (ACT) in Worcester, Mass., claimed it had developed just such a procedure. The company touted it as a way around the firestorm of controversy surrounding the conventional technique for growing these cells, which destroys human embryos. Most researchers find the method intriguing, because it might lead to new and maybe better stem cell lines. But several also argue that it raises fresh dilemmas.

Scientists investigate human embryonic stem cells because they can become any other kind of cell. As such, they hold great promise in regenerating body parts. Conventionally, researchers rely on embryos produced during in vitro fertilization (IVF) attempts, removing the inner cell mass from embryos that have grown to 50 to 100 cells. Currently at least 400,000 frozen embryos lie unused in U.S. fertility clinics, and thousands are typically discarded annually.

ACT's vice president of research and scientific development, Robert Lanza, and his colleagues experimented with 16 unused human embryos from an earlier, eight- to 10-cell stage. Physicians routinely pluck single cells from IVF embryos at that stage for preimplantation genetic diagnosis (PGD), which scans these cells, known as blastomeres, for diseases. Embryos can compensate for the loss and have so far developed into some 1,500 apparently healthy children since this procedure was introduced more than a decade ago.

Starting with a technique similar to PGD, the ACT researchers used micro eyedroppers to extract 35 blastomeres one or two at a time from the six highest-grade embryos they had. They then generated two stable human embryonic stem cell lineages, which they reported online August 23 via Nature. These cell lines apparently behave like their conventional counterparts, capable of replicating for months on end and developing into other cell types.

ACT ended up destroying its embryos--to make the most of the few embryos it had, Lanza's team eviscerated them by taking several cells from each (up to seven). But because standard PGD does not kill the embryo, the scientists declared that their method in principle can deliver stem cell lines without killing the embryos. Researchers regard the cells generated by this method as scientifically intriguing, because they come from earlier-stage embryos. Development neurobiologist Arnold Kriegstein of the University of California, San Francisco, noted that the 50- to 100-cell-stage embryo cell lines cannot split to become twins, whereas eight- to 10-cell-stage embryos such as those ACT used can. It suggests that the younger cells "might have better potential for turning into certain kinds of tissue than currently used lines," he says. "Only further experiments will tell."

Even if investigators can get the method to work, however, the controversy will not abate. It remains uncertain whether single human blastomeres could develop into living beings. If they can, this technique would land the cell lines back in the original controversy. "In sheep and rabbits, for example, single cells are capable of developing into viable animals; however, the same does not appear to be true for mice," said James Battey, chair of the National Institutes of Health stem cell task force, at a Senate hearing in September.

In addition, the ACT study has already destroyed 16 embryos. Hence, whether the method can add to the number of federally funded human embryonic stem cell lines is unclear, the U.S. President's Council on Bioethics reported, because the law prevents funding of any additional lines produced through the destruction of embryos. Lanza says that ACT probably would file for federal funding to continue the work. The company has announced that--with the WiCell Research Institute in Madison, Wis., which hosts the National Stem Cell Bank--it would distribute ACT's new cell lines to U.S. scientists, provided that the federal government will fund research using them.

In the end, even if ACT overcomes the technical and ethical issues, it may face one last obstacle: resistance from physicians and expectant parents. In the Nature paper, the extracted cells were not grown in isolation but incubated near one another to help them thrive from chemical signals they each release. (A single blastomere isolated from other cells is less likely to lead to a cell line.)

Lanza says that ACT has some evidence that lone blastomeres placed next to the embryos from which they were extracted could grow without risk to the embryos. But whether such assurance would be good enough for IVF doctors and their patients is not clear, points out IVF gynecologist Outi Hovatta of the Karolin¿ska Institute in Sweden. They may not want to take any chances with their future children, even if ACT ultimately becomes ready, willing and able.

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