Injecting embryonic stem cells (ESCs) into female mice partially
corrects congenital heart defects in their future offspring, a new study
has found, suggesting that stem cells may be able to cure genetic defects
indirectly.
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ESCs are primitive, unspecialised cells which have the potential
to develop into any cell in the body – so they could theoretically be used
to replace damaged cells and tissues. But the new study, led by Diego Fraidenraich
of the Memorial Sloan-Kettering Cancer Center, New York, US, suggests ESCs
could also help treat congenital diseases by releasing growth factors.
Where the ESCs were injected into female mice that later became pregnant,
the cells did not cross the placenta and so appeared to cure the congenital
defect “from a distance”.
“Cells in the abdomen of the treated mothers were secreting factors
that crossed the placenta,” says Robert Benezra, one of the study’s authors.
It was these proteins, or factors, that partially corrected the defect.
Injecting embryonic stem cells (ESCs) directly into mouse embryos
predisposed to the same fatal heart defect completely protected them against
the disorder, the team found.
Correcting neighbours
The researchers believe there are two factors responsible for these
effects: IGF-1 acts over a long range and can cross the placenta, whereas
WNT5a acts locally and so had an effect only when the stem cells were injected
directly into the embryo.
“People have known for some time that [stem cells] can act as replacement
cells,” says Benezra. “Now it seems they are also capable of correcting their
neighbours.”
However, it may not be realistic to apply this technique to a congenital
heart defect in human embryos. “You would have to know you have a mutant
blastocyst [early embryo],” says Robin Lovell-Badge, a stem cell expert at
the National Institute of Medical Research in London.
A test for a mutant blastocyst could be done by taking a biopsy
of one or two cells from an eight-cell embryo. But if a mutant was found it
could be screened out in favour of a normal embryo, he says.
Powerful potential
Injecting into the abdomen of the human mother is also unlikely
to work, he says. “If you inject embryonic stem cells into the peritoneal
cavity they will tend to form a tumour,” he told New Scientist.
Kenneth Chien at the University of California San Diego, who wrote
a perspective article to accompany the paper, agrees. “The importance isn’t
therapeutic,” he says. He believes the work could be useful indirectly.
ESCs could be used to identify factors that can correct congenital
heart defects in humans, just as Fraidenraich and his colleagues were able
to show the factors responsible in mice were IGF-1 and WNT5a, he adds.
And instead of administering stem cells to the mother, it may be
possible to partially correct heart defects in offspring by providing her
with the necessary factors. A similar approach could treat adult heart disease
without stem cells being added to the adult heart tissue.
The technique has revealed much about the potential of stem cells.
“It makes them more powerful than we had previously assumed,” says Benezra.
Journal reference: Science (vol 306, p 247)
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