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Baby to Brain

Therapy clues from fetal cells that enter mom's brain.
FETAL CELLS



"FETAL MICROCHIMERISM IN THE MATERNAL MOUSE BRAIN," BY XIAO-WEI TAN ET AL. IN STEM CELLS ONLINE; AUGUST 10, 2005
Mothers could literally always have their kids on their minds. Researchers find that in mice, cells from fetuses can migrate into a mother's brain and apparently develop into nervous system cells.

The discovery comes from Gavin S. Dawe of the National University of Singapore and Zhi-Cheng Xiao of Singapore General Hospital, along with their colleagues from China and Japan. They were looking to design therapies for stroke or diseases such as Alzheimer's. Scientists have known for years that fetal cells can enter a mother's blood; in humans, they may remain there at least 27 years after birth. Like stem cells, they can become many other kinds of cells and in theory might help repair damaged organs.

The neurobiologists bred normal female mice with males genetically modified to uniformly express a green fluorescent protein. They found green fetal cells in the mothers' brains. "In some regions of some mothers' brains, there are as many as one in 1,000 to sometimes even 10 in 1,000 cells of fetal origin," Xiao reports.

The fetal cells transformed into what seem like neurons, astrocytes (which help to feed neurons), oligodendrocytes (which insulate neurons) and macrophages (which ingest germs and damaged cells). Moreover, after the scientists chemically injured the mouse brains, nearly six times as many fetal cells made their way to damaged areas than elsewhere, suggesting the cells could be responding to molecular distress signals released by the brain.

Just how the fetal cells make it through the capillaries separating the brain from the blood system is not known--the cells of the vessels are densely packed, preventing most compounds from crossing the barrier. The researchers speculate that biomolecules such as proteins or sugars adorning fetal cell surfaces interact with the blood-brain barrier and allow the cells to wriggle past. The team feels confident that fetal cells can also pass to the brains of males and nonpregnant females, given little evidence of major differences between their blood-brain barriers and those of pregnant females, Dawe says. The scientists hope next to show that the fetal cells become functional neurons.

The finding, published online August 10 by Stem Cells, gives fresh hope in treating brain disorders. Because of the blood-brain barrier, transplant therapies for the brain normally evoke thoughts of drilling into the skull. Identifying the molecules typical of fetal cells that enter the brain and become nervous system cells could help find similar cells from sources other than fetuses, such as umbilical cord blood. Such research could lead to noninvasive cell transplants for the brain requiring only intravenous injections. Any cells used for therapies would be matched to patients as closely as possible to avoid triggering immune disease. It remains uncertain whether injected cells meant for the brain could end up grafting somewhere else, "but we don't know yet if that happening would even be a problem," Dawe says.

The investigators are also now looking to see if the passage of fetal cells to the brain occurs in humans as readily as it does in mice. They plan on looking at postmortem brain tissue from mothers of boys. Signs of a Y chromosome would confirm the effect in humans. It would also, Xiao points out, raise the issue of "whether there are any behavioral or psychological implications."

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