Cloned stem cells prove identical
to fertilized stem cells
CAMBRIDGE, Mass. (January 17, 2006) - Scientists generally
agree that all cloned animals are biologically flawed.
But they don't agree about what that means for stem
cells derived from cloned embryos, the basis for therapeutic
cloning.
Also known as somatic cell nuclear transfer, therapeutic
cloning is a promising approach to create individually
customized cellular therapies for treating certain disorders.
Demonstrated in mice but not in humans, it begins with
stem cells derived from a cloned embryo. But if cloned
embryos can't produce normal organisms, how can they
produce normal stem cells?
Analyzing the complete gene-expression profiles of both
cloned and fertilization-derived stem cells in mice,
scientists at Whitehead Institute for Biomedical Research
now have concluded that the two are, in fact, indistinguishable.
"In my opinion, these results solidify the
argument that while a cloned animal is abnormal,
a cloned stem cell is perfectly normal," says
Whitehead Member Rudolph Jaenisch. |
"This paper demonstrates clearly that it doesn't
matter if a stem cell has been derived from a cloned
embryo or from a fertilized embryo," says Whitehead
Member Rudolf
Jaenisch, senior author on the paper that will appear
online the week of January 16 in the Proceedings
of the National Academy of Sciences. "Both
can be equally good for therapy."
To create a clone, a scientist removes the nucleus from
a donor cell, then places it into an egg from which
the nucleus has been removed. The researcher then tricks
the egg into thinking it's been fertilized. The egg
develops into a blastocyst, an early stage embryo consisting
of no more than 100 or so cells. The scientist can then
either remove the stem cells from this blastocyst, or
place it into a uterus where it has the potential to
develop into a fetus.
Here's where things get complicated. The original donated
nucleus may have come from, say, a skin cell. For a
viable fetus to develop, the egg needs to reprogram
the genome of the skin cell, shutting off genes specific
for skin tissue and turning on genes needed for embryonic
development, genes that are normally dormant in tissue-specific
cells. In other words, the egg needs to erase all tissue-specific
memories from the skin cell and revert it into a genomic
blank slate.
But this entire process is almost never perfect, and
nearly all cells in a cloned blastocyst retain some
memory of their original source. As a result, the developing
fetus inevitably has some degree of genetic abnormality.
Most clones, in fact, die in utero or at birth. The
few clones that make it into adulthood are often plagued
by bizarre health complications. This is one reason
why scientists generally believe that attempting to
clone a human being is morally reprehensible.
But are the cloned embryo's stem cells beleaguered by
the same defects?
Studies have demonstrated that a small number of stem
cells in the blastocyst appear to be spared this faulty
reprogramming. When stem cells from a cloned blastocyst
are removed and placed into a dish, most die. A few,
however, survive and give rise to an embryonic stem
cell line, and these appear to be thoroughly reprogrammed.
Researchers have tried to test the integrity of these
surviving stem cells by transplanting them into fertilized
blastocysts and then observing the overall health of
the resulting animal. Although these animals generated
entirely from cloned stem cells appear to be fine, many
scientists don't accept this result as definitive.
Tobias Brambrink, a postdoctoral researcher in the Jaenisch
lab, tried a different approach, comparing gene expression
in cloned and fertilization-derived stem cells. With
a series of microarray chips, Brambrink measured which
genes were active and which were silent in both kinds
of cells. To ensure the accuracy of his results, he
compared five lines of cloned stem cells with five fertilization-derived
stem cell lines.
"The results are very clear," says Brambrink.
"If a gene is active in fertilized stem cells,
it's also active in cloned stem cells, and at the same
level of activity. The same goes for genes that are
silent. There is really no significant molecular difference
between both kinds of stem cells."
"In my opinion, these results solidify the argument
that while a cloned animal is abnormal, a cloned stem
cell is perfectly normal," says Jaenisch.
This study was funded by the National Institutes of
Health.
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