Embryonic Stem Cell Success
In Mouse Experiment, Cells From Testes Are Transformed
By Rick Weiss
Washington Post Staff Writer
Saturday, March 25, 2006; Page A11
Scientists in Germany said yesterday that they had retrieved easily obtained
cells from the testes of male mice and transformed them into what appear to
be embryonic stem cells, the versatile and medically promising biological
building blocks that can morph into all kinds of living tissues.
If similar starter cells exist in the testes of men, as several scientists
yesterday said they now believe is likely, then it may not be difficult for
scientists to cultivate them in laboratory dishes, grow them into new
tissues and transplant those tissues into the ailing organs of men who
donated the cells.

The technique would have vast advantages over the current approach to
growing "personalized" replacement parts -- an approach that has stirred
intense political controversy because it requires the creation and
destruction of cloned human embryos as stem cell sources. The new work
suggests that every male may already have everything he needs to regenerate
new tissues -- at least with a little help from his local cell biologist.
No one knows whether cells with similar potential exist inside female
bodies -- a crucial question if women, too, are to have access to new
tissues genetically matched to themselves and so not susceptible to
rejection by her immune system. But recent studies have led many researchers
to conclude that the possibility is greater than previously believed.
"We may not be as successful in getting the same result in humans as in
mice," said study leader Gerd Hasenfuss, a cardiologist at
Georg-August-University of Goettingen. "But I am very much convinced that
this is the basis for a therapeutic strategy. I am optimistic."
Other scientists said the findings are exciting but reiterated Hasenfuss's
first point, noting that mice have been cured of many diseases that still
kill humans every day.
"The major caveat is that this was done in mice, and unfortunately we're
starting to learn there really is a difference between mouse and human,"
said Evan Snyder, director of the stem cell program at the Burnham Institute
in San Diego.
Embryonic stem cells are among the earliest cells to appear in newly
developing organisms and have the potential to become every kind of cell or
tissue in the body. In recent years, scientists have learned to keep them
alive in laboratory dishes and, by adding certain nutrients or hormones,
coax them to become pancreatic cells, cardiac cells, nerve cells or others
that may someday serve as living "patches" for patients with diabetes, heart
disease, spinal cord injuries or other degenerative conditions.
The new report, published yesterday in the online edition of the journal
Nature, is not the first claimed discovery of an alternative source of
embryonic stem cells. But previous claims, including the purported discovery
of such cells in everything from menstrual blood to bone marrow to fat, have
suffered from incomplete evidence for their biological versatility, or have
proved to be too rare or difficult to isolate to be of practical value.
By contrast, the new work involves cells that were numerous and easy to
find; if they exist in men, Hasenfuss said, they could probably be obtained
with biopsy techniques routinely used in male fertility studies. And the
cells passed every gold-standard test used today to prove their equivalence
to embryonic stem cells.
"The evidence presented looks very good indeed, and we should welcome this
new advance in stem cell research and the possibilities that it opens up,"
said Allan Spradling, a Howard Hughes Medical Institute investigator who
studies early development at the Carnegie Institution of Washington.
Hasenfuss, with study co-leaders Wolfgang Engel and Kaomei Guan, isolated
from mouse testes "spermatogonial stem cells," which are the mother cells
that give rise to a steady supply of sperm throughout a male's life. They
showed that under carefully controlled conditions, those cells can become
"multipotent adult germline stem cells" that share all the characteristics
of embryonic stem cells.
They can make countless copies of themselves, for example, and under the
right conditions will morph into any kind of body cell. Among others,
Hasenfuss has already grown liver cells, muscle cells, pancreas cells,
dopamine-secreting nerve cells (the kind that die off in Parkinson's
disease) and various kinds of heart cells, which spontaneously coalesced in
a lab dish and started beating in synchrony.
German scientists have great incentive to find alternatives to human
embryonic stem cells, because government restrictions on human embryo cell
research there are even more severe than they are in the United States,
where federally funded scientists are banned from working on embryonic stem
cell colonies created after August 2001.
Still, Hasenfuss said he favors scientists' being allowed to pursue both
embryonic cells and alternatives until it is clear which avenue shows the
most medical promise.
As an aside, he noted that the editors at Nature demanded many additional
tests and an unusually thick pile of documentation before accepting his
report for publication -- a result, he said, of the embarrassment that its
sister journal, Science, recently faced when seemingly monumental stem cell
studies by Korean researcher Hwang Woo Suk proved to have been faked.
Rudi Jaenisch, a stem cell researcher at the Whitehead Institute for
Biomedical Research in Cambridge, Mass., said he found the new report
"pretty convincing" but warned that further studies would be needed to show
that the cells remain normal over time. His main concern is that
sperm-producing cells often bear molecular "imprints" that can interfere
with their ability to produce normal tissues.
Hasenfuss said that he had not tested for those imprints yet but that the
tissues so far appear normal.
Until recently, it was thought that girls are born with all the egg cells
they will ever have, which would suggest that female equivalents of
Hasenfuss's testicular cells don't exist. But a Harvard team last year found
evidence of egg production in adult mice, suggesting that egg precursor
cells similar to Hasenfuss's sperm-producing cells may be housed in women's
ovaries. If so, Hasenfuss said, they too may be able to become embryonic
stem cells.

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