Baby comes with brain repair kit for mum

Everyone knows that kids get their brains, or lack of them, from their parents. But it now seems that the reverse is also true. Stray stem cells from a growing fetus can colonise the brains of mothers during pregnancy, at least in mice. If the finding is repeated in humans, the medical implications could be profound. Initial results suggest that the fetal cells are summoned to repair damage to the mother’s brain. If this is confirmed, it could open up new, safer avenues of treatment for brain damage caused by strokes and Alzheimer’s disease, for example.

This is a long way off, but there are good reasons for thinking that fetal stem cells could one day act as a bespoke brain repair kit. It is already well known that during pregnancy a small number of fetal stem cells stray across the placenta and into the mother’s bloodstream, a phenomenon called microchimerism. They can survive for decades in tissues such as skin, liver and spleen, where they have been shown to repair damage.

Nature’s ploy to “treat mother” makes evolutionary sense too, because the fetus has a better chance of survival if the mother is fit and healthy both during and after pregnancy. But nobody has seen this effect in brain cells. “This is the first study to show conclusively that fetal cells cross the blood-brain barrier,” says Diana Bianchi, a world authority on microchimerism at Tufts University School of Medicine in Boston, Massachusetts. A team led by Gavin Dawe of the National University of Singapore and Xiao Zhi-Cheng of Singapore’s Institute of Molecular and Cell Biology showed that once the stowaways enter mouse brains, they mature into different cell types.

These include cells resembling neurons, which transmit electrical impulses; astrocytes, which support neurons; and oligodendrocytes, which ensheath and protect nerve cells. “They can become almost all major cell types found in the brain,” Dawe says. The researchers have not yet demonstrated whether the cells are functional, however. “We need to know, for example, whether fetal cells expressing characteristics of neuronal cells can actually fire action potentials and synapse with native cells in the mother’s brain,” he adds. “There are good reasons for thinking that fetal stem cells could one day act as a bespoke brain repair kit.” To make fetal stowaways easy to spot in samples from the mother’s brain, Dawe and Xiao mated normal female mice with male mice genetically engineered so that their cells contained a fluorescing protein derived from jellyfish, making the cells glow bright green.

This revealed that the fetal cells did not spread evenly. When the researchers induced stroke-like injuries to the brains of some of the mother mice, the fetal cells became six times more concentrated at the damaged areas, suggesting they may be involved in repair. Dawe says it is not yet clear how they are summoned to the sites of injury, but he suspects they are drawn there by “SOS-like” signalling factors from damaged tissue. The team is also trying to identify surface molecules unique to the brain-bound fetal cells, and hopes to isolate human counterparts from umbilical blood or bone marrow. This would be vital for medical applications, as a large number of cells might be needed to have any medical effect. “It would be important to enrich for ones that can cross the blood-brain barrier,” Dawe says.

A big potential advantage of using fetal cells as a treatment is that they could simply be injected into the bloodstream and left to find their own way into the brain. This would make it possible to treat conditions with diffuse injury, such as Alzheimer’s disease. The only existing way of getting cells into the brain to treat injured or defective areas is to inject them directly through the skull into the area where they are required. Parkinson’s disease, for example, has been treated by injecting cells that make the neurotransmitter dopamine into the region of the brain that fails to make the substance in Parkinson’s patients. Some researchers have shown, however, that injected fetal cells are capable of migrating across the brain to sites of damage.

“A big potential advantage is that cells could simply be injected into the blood and left to find their own way to the brain. ”Dawe and Xiao warn that it could take anything from five to 20 years to develop treatments, not least because in some cases, fetal cells have been shown to aggravate immunological disease. “It’s important we know it’s safe and of benefit before we try it in patients,” Dawe cautions. One key step will be to establish beyond doubt that the effect seen in mice happens in humans too. Dawe says this can be done by looking for cells containing a Y chromosome in post-mortem brain tissue from mothers of boys. “We’ve already started work on acquiring tissue to answer this question,” he says.

Bianchi says that most research on microchimerism in mice has later been borne out in humans. “In every aspect, the trend has been the same,” she says. But even if the phenomenon does occur in people, there are many hurdles to be cleared on the way to developing treatments. “It’s unclear how long the newly arrived cells will live, and how well they would integrate into the specialised functional networks of the brain,” says Jakub Tolar, a specialist in microchimerism at the University of Minnesota in Minneapolis. “Predictions of clinical use must come with caution and reflection.”

New Scientist
September 13, 2005

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