Cells That Go Back in Time
Lop off a newt's leg or tail, and it will grow a new one. The creature's cells can regenerate thanks to built-in time machines that revert cells to early versions of themselves in a process called dedifferentiation.
Researchers who study this mechanism hope one day to learn how to induce the same "cell time travel" in humans. If the cells go back far enough, they become stem cells, which researchers believe hold promise for treating many diseases. Stem cells, which are often taken from embryos, are unformed and have the ability to become many different types of cells. If researchers succeed in inducing this cell time travel, they will also eliminate the ethical issues surrounding embryonic stem-cell research, because no embryos would be destroyed to obtain the cells.
The research is in its infancy, but a 2001 discovery jump-started the field of study. Mark Keating, Christopher McGann and Shannon Odelberg applied a protein extract derived from newts to mouse muscle cells. To their surprise, the protein extract transformed those muscle cells into stem cells in just 48 hours, which means the mouse cells would have the ability to regenerate.
No one expected the experiment to work. Previously, scientists believed that once mammalian cells became muscle, bone or any other type of cells, that was their fate for life -- and if those cells were injured, they didn't regenerate, but grew scar tissue.
But Keating's experiment introduced the possibility that, under the right circumstances, humans -- who are 99 percent genetically similar to mice -- might one day be able to regenerate their own cells. Those regenerated cells could be used to treat disease.
"For those of us who want to understand what happens in dedifferentiation, our ultimate goal is to be able to form a pool of stem-cell-like cells that would be able to repopulate the organ or tissue you're trying to repair," said Catherine Tsilfidis, a scientist at the Ottawa Health Research Institute who has reproduced Keating's findings, which she describes as "beautiful."
In newts and some other animals with the ability to regenerate, cells at the site of an injury can revert to their embryonic stem-cell stage and can become another type of cell in that creature's body. In other words, a skin cell can dedifferentiate into a stem cell, then regenerate into a muscle cell or another completely different type of cell.
Tsilfidis and her colleagues are now trying to pinpoint which genes are responsible for kick-starting newt dedifferentiation. They published findings in the March 23 issue of Developmental Dynamics identifying 59 DNA fragments that seem to play a role in newt forelimb regeneration, and Tsilfidis believes many of those gene fragments have counterparts in humans.
"Whether (those genes) can actually induce dedifferentiation is yet to be determined," Tsilfidis said. While the genes were active during maximum dedifferentiation activity, she said, so much is going on in cells after a newt's forelimb is cut off that it's difficult to pick out specific dedifferentiation genes.
While some cells are dedifferentiating, others have already begun regenerating and differentiating, or becoming specialized cells. They're performing activities like healing wounds or growing blood vessels, so it's difficult to pin certain genes to specific activities.
Adult human bodies do contain some stem cells, but they are rare.
"Maybe only one in a million cells in a particular region might have that regenerative capacity you're interested in," said Robert Naviaux, who studies cancer and stem-cell differentiation, and is co-director of the Mitochondrial and Metabolic Disease Center at the University of California at San Diego. "Stem cells are more concentrated in certain locations like human umbilical cords, blood and bone marrow, and certain areas of the brain around the ventricles."
People who believe it's unethical to destroy any embryos, even those abandoned and destined for destruction at in vitro fertilization clinics, have touted adult stem cells as an ethical choice. The field has seen some success, but many researchers believe adult stem cells have less "plasticity," or ability to become different types of cells.
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But at least one religious leader believes the ability to use dedifferentiation to create human stem cells would eliminate the controversy.
"I believe that dedifferentiation -- the direct conversion of a somatic cell into an embryonic stem cell -- is the holy grail for those seeking morally acceptable alternatives to the destructive embryo research now required to obtain (embryonic stem) cells," said Father Nicanor Austriaco, a molecular biologist and Catholic priest in Washington, D.C. "You would also be able to get immunocompatible (embryonic stem) cells from every patient by simply dedifferentiating his or her cells. This would be an amazing discovery."