[Paleopsych] Cells That Go Back in Time

[Steve Hovland]

By Kristen Philipkoski </news/feedback/mail/1,2330,0-31-67155,00.html>  
</news/feedback/mail/1,2330,0-31-67155,00.html> |  Also 
</news/storylist/0,2339,31,00.html> by this reporter  Page 1 of 1
02:00 AM Apr. 08, 2005 PT
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 
<http://www.pnas.org/cgi/content/abstract/98/24/13699> jump-started the 
field of study. Mark Keating 
<http://www.hhmi.org/research/investigators/keating.html>, 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 <http://www.ohri.ca/profiles/tsilfidis.asp>, 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 <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=  
pubmed&dopt=Abstract&list_uids=15789445> 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.
Researchers are trying to learn similar lessons from other creatures that 
have the ability to regenerate, including starfish 
<http://www.vsf.cape.com/~jdale/science/regeneration.htm>, zebrafish 
<http://www.hhmi.org/news/keating5.html>, earthworms and lobsters.
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 
<http://biochemgen.ucsd.edu/mmdc/staff.htm>, 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.
Others have promoted various schemes </news/medtech/0,1286,66113,00.html> 
for getting around the embryo conundrum, but none has received a unanimous 
stamp of approval from scientists and religious groups or others who oppose 
the destruction of embryos.
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 
<http://db.yeastgenome.org/cgi-bin/colleague/colleagueSearch?id=197>, 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."