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Stem cells mend hearts at a distance

19:00 07 October 04

http://www.newscientist.com/news/news.jsp?id=ns99996505

NewScientist.com news service

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.

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 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, according to researchers.

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 they 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.

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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