Building brand new kidneys

Advanced Cell Technology has sparked yet more controversy with its claim to have grown kidney-like organs.

By | February 13, 2002

NEW YORK — The Massachusetts-based biotechnology company Advanced Cell Technology (ACT) recently announced that it has used cells derived from cloned cow embryos to grow kidney-like organs that function and are not rejected when implanted into adult cows. This marks the first use of cloning technology to grow personalized, genetically matched organs for transplantation.

But like some of the other results announced by ACT during the past year, this latest research has not been published in a leading scientific journal or confirmed by others. And although the kidney-like organs can apparently remove toxins from the body and produce urine, it's not known whether they can perform all of the many jobs for which kidneys are responsible.

Last year, ACT created a worldwide stir when it announced it had conducted experiments to clone human embryos. This experiment was published in e-biomed: The Journal of Regenerative Medicine. The paper immediately drew a lot of criticism, not least because it was not published in a well-known journal, although it was peer reviewed before electronic publication. Now there is a chorus of detractors who point to serious flaws in the experiment. One of the group's earlier experiments involving the cloning of monkey embryos was taken seriously in academic circles largely because it was published in the journal Science (Science 2002, 295:819).

If the company's latest approach can be used to make human kidneys from cloned human embryos — as the Massachusetts team expects — it could dramatically reduce the need for donor kidneys and transplants in the future. "We can say clearly that these kidneys produced urine and survived for several months inside the cows," said Robert Lanza, chief scientist on the project at ACT. But ACT's latest accomplishment — first reported in the US in the Washington Post newspaper — is also suspect in scientific circles because the company chose to announce it through a press conference, rather than through peer-reviewed publication or a presentation at a scientific meeting. Lanza said he released the data to the WashingtonPost to correct errors in articles published by London newspapers on the work. He said the research is being written up for publication in a journal.

The work is "proof of principle that therapeutic cloning can work," said Lanza. As the replacement tissues would be genetically identical to the patient, they would not be rejected by the patient's immune system. Jose Cibelli, chief scientist at ACT, said the company's main goal is this kind of therapeutic cloning: to create embryo-stage clones of ill people, and then treat the patient with cells derived from those embryos. But the approach is controversial because it requires the production and preordained destruction of cloned human embryos.

The ACT team produced embryos using a standard cloning technique, replacing the DNA of a cow's egg with that taken from the skin cell of another cow's ear. Because they did not know how to manipulate embryonic stem cells from cows, they let the cow embryos develop into fetuses, Lanza explained. Then, working with researchers from Children's Hospital in Boston, they placed the immature cells on a five-centimeter-long support structure that resembled a sponge. The cells grew on the structure and took on the function of a kidney. Lanza said his team implanted several of these under the skin of the cow that donated the original skin cell. There they produced urine that was collected in bags.

He said the company chose to do the experiment with a cow instead of a mouse, for example, because the cow is a large animal with a sophisticated immune system similar to a human's. Other kidneys derived from fetal cells that had not been cloned failed, suggesting that they had been rejected by the recipient cow's immune system.

This latest experiment is likely to further polarize the debate over embryonic stem cell research and human cloning. The use of bovine fetuses will play into fears that scientists are trying to grow clones for direct harvesting of body parts. Some in the US consider research on human embryo clones inherently unethical and have been calling for a federal ban on such work. But others believe that such objections might be outweighed if the research were shown to be the most promising means of growing replacement tissues. Last year the US House of Representatives passed a bill banning both the production of cloned human babies — reproductive cloning — and cloned human embryos for medical research — therapeutic cloning. The US Senate is considering whether to pass an identical bill or a more narrowly worded one that would outlaw only reproductive cloning.

The latest research remains preliminary but the cow study is the first to indicate that cells taken from a newly created clone can be made to grow and work together as an apparently functioning organ and coexist with the body's immune system. Research published last year by a different group in the Journal of Pathology suggests that less ethically contentious adult stem cells may have the same potential as embryonic cells. And some scientists worry about the broader implications of the ACT work. "This is skating very close to a line that is sending the wrong message of what we are trying to do with stem cells," suggested John Gearhart, a stem cell expert at Johns Hopkins University. "This is not going to be an acceptable procedure we can do" in humans, he concluded.

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