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Human Brain Cells Are Grown In Mice

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The guidelines allow for a slow scale-up of the proportion of human cells in animals' brains. Gage estimated that in the latest work as few as 100 of the 100,000 injected cells survived and became integrated with the mouse brains, which typically contain 75 million to 90 million mouse cells.

Henry Greely, a Stanford law professor and ethicist who has reviewed proposals to create human-mouse chimeras, said the work looked "interesting, good and ethical" by current standards.

Stem cell therapies "will only work if the transplanted cells will make those connections," Greely said, "and there's no better place to test that but in an animal model."

In painstaking surgeries conducted on a small, heated operating platform, Gage and his co-workers, including Alysson R. Muotri and Kinichi Nakashima, partially removed 14-day-old mouse fetuses from the womb, being careful not to disrupt the placenta that provides maternal nourishment. After injecting the human stem cells into curved cavities of the brain called the lateral ventricles, they tucked the pups back in for their last week of development.

The human cells, taken from days-old human embryos by a San Diego company, CyThera Inc., had been engineered to emit a green fluorescence. That helped them stand out against the mouse cells when the animals' brains were later analyzed under the microscope.

Although embryonic stem cells have sometimes turned into tumors in other experiments, no such growths developed, Gage said. Nor were they rejected by the mice's immune systems, perhaps because they were injected so early that they were perceived as "self" rather than "other."

The cells migrated into the forebrain, where they grew only to the size of mouse neurons. Most extraordinary, Gage said, was that they connected to others and were firing -- though it is still unclear if they fire in electrical patterns typical of mouse or human cells.

One possible application, Gage said, would be to place healthy human cells in the brains of mice that have versions of human neuronal diseases, such Alzheimer's, Lou Gehrig's or Parkinson's, and see how the neurons fare.

That experiment might reveal whether those diseases have their roots elsewhere and subsequently affect neurons, or whether they emerge directly from ill neurons, in which case the human cells would remain unaffected.


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