Mouse tails grow mice

Several teams of scientists activate genes to create cells indistinguishable from embryonic stem cells

June 07, 2007|By Karen Kaplan | Karen Kaplan,Los Angeles Times

Scientists have succeeded in reprogramming ordinary cells from the tips of mouse tails and rewinding their developmental clocks so they are virtually indistinguishable from embryonic stem cells, according to studies published today.

If the discovery applies to human cells - and researchers are optimistic that it will - it would offer a straightforward method for creating a limitless supply of cell lines tailor-made for patients without ethical strings attached.

Three research groups said they accomplished their feat by activating four genes that are turned on in days-old embryos. Some of the rejuvenated cells grew into new mice, demonstrating the cells' ability to create every type of tissue in the body.

"This is truly the Holy Grail - to be able to take a few cells from a patient, say a cheek swab or some skin cells, and turn them into stem cells in the laboratory," said Dr. Robert Lanza, an embryonic stem cell researcher and head of scientific development at Advanced Cell Technology Inc. in Worcester, Mass., who was not involved in the research.

MIT biologist Rudolf Jaenisch, who worked on two of the studies, said there are still "lots and lots of technical hurdles to overcome." Some of the thorniest problems might take years to resolve despite the fact that mice and humans share many fundamental aspects of cell biology.

But if those hurdles are cleared, reprogrammed cells could become the long-sought substitute for embryonic stem cells, which are at the heart of the nascent field of regenerative medicine.

President Bush and other social conservatives have long opposed human embryonic stem cell research because the cells can be obtained only by destroying embryos.

Government funding of such research is a top political issue in Washington. The House is scheduled to vote on the issue today.

Reprogrammed cells could enable scientists to sidestep the ethical dilemmas surrounding a contentious area of research known as therapeutic cloning, in which scientists seek to create a human embryo that is genetically identical to a sick patient by inserting the patient's DNA into an unfertilized egg.

The resulting stem cells harvested from the embryo could theoretically be used to generate neurons for patients with Parkinson's disease or insulin-producing cells for diabetics without the risk of tissue rejection.

Stem cells derived from reprogrammed cells would enable scientists to create genetically matched tissues without having to create and destroy a cloned human embryo.

Japanese researchers made substantial progress last year in turning back the clock on adult cells, publishing an influential study in which cells from the tails of adult mice were reprogrammed to become "pluripotent" - able to grow into many kinds of tissues.

"Nobody believed it," said Kathrin Plath, a researcher with the Institute for Stem Cell Biology and Medicine at UCLA who set out to replicate the findings with colleagues at UCLA, Harvard and MIT.

In one of the new studies, published in the journal Nature, the Japanese scientists found that when modified cells - dubbed induced pluripotent stem cells, or iPS cells - were injected into mouse embryos, they contributed to the development of all parts of the animal.

Some of their offspring also inherited genes from the iPS cells. Senior author Dr. Shinya Yamanaka, from Kyoto University's stem cell biology department, said that genetic inheritance was an important sign because only cells that behave like embryonic stem cells can be passed from parent to child.

Meanwhile, Plath's group tweaked the Japanese recipe and gathered additional evidence. Their study was published in the journal Cell Stem Cell.

The team studied the pattern of genes turned on and off in the iPS cells and embryonic stem cells; they found the patterns were nearly identical.

The third group, led by Jaenisch at the Whitehead Institute for Biomedical Research in Cambridge, Mass., injected mouse embryos with iPS cells and tagged some of the genes. Then they bred the resulting pups with other mice.

The researchers figured that if the tagged genes were functioning like embryonic stem cells, the offspring had a 50-50 chance of inheriting them.

It turned out that five out of nine animals had inherited the reprogrammed cells in their bodies, according to a study in Nature.

Karen Kaplan writes for the Los Angeles Times.

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