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By injecting stem cells directly into the brain, scientists have successfully reversed neural birth defects in mice whose mothers were given heroin during pregnancy. Even though most of the transplanted cells did not survive, they induced the brain’s own cells to carry out extensive repairs.

Transplanted stem cells have previously shown promise in reversing brain damage caused by strokes, as well as by neurological diseases like Parkinson’s, Alzheimer’s, and Huntington’s. But their use in treating birth defects is relatively new. In recent years, a handful of research teams have been developing stem-cell-based therapies for rodents with real or simulated birth defects in the brain.

Joseph Yanai, director of the Ross Laboratory for Studies in Neural Birth Defects at the Hebrew University-Hadassah Medical School, in Jerusalem, says that stem-cell therapies are ideal for treating birth defects where the mechanism of damage is multifaceted and poorly understood. “If you use neural stem cells,” says Yanai, “they are your little doctors. They’re looking for the defect, they’re diagnosing it, and they’re differentiating into what’s needed to repair the defect. They are doing my job, in a way.”

Yanai and his colleagues began with mice that had been exposed to heroin in the womb. These mice suffer from learning deficits; when placed in a tank of murky water, for instance, they take longer than normal mice to find their way back to a submerged platform. And in their hippocampus–an area of the brain associated with memory and navigation–critical biochemical pathways are disrupted, and fewer new cells are produced.

All of those problems are swiftly resolved when the researchers inject neural stem cells derived from embryonic mice into the brains of the heroin-exposed animals. When swimming, the treated mice caught up with their normal counterparts, and their cellular and biochemical deficits disappeared. Yanai announced these findings in 2007 and 2008.

Such dramatic results were surprising, considering that just a fraction of a percent of the transplanted stem cells survived inside the mice’s brains. But they are consistent with an emerging consensus of how adult stem cells perform their many functions through so-called bystander or chaperone effects. Beyond simply generating replacements for damaged cells, stem cells seem to produce signals that spur other cells to carry out normal organ maintenance and initiate damage control.

“The chaperone effect is an important aspect of stem-cell biology that’s simply been under-recognized,” says Evan Snyder, who directs the Stem Cell Research Center at the Burnham Institute for Medical Research, in California, and whose research group coined the term in 2002. “That actually may be the low-hanging fruit in the stem-cell field–taking advantage of this, and not the cell-replacement aspect that we always thought would be the key to stem-cell biology in regenerative medicine.”

Cesar Borlongan, a professor and vice chairman for research in the department of neurosurgery at the University of South Florida College of Medicine, uses a different model to explore the use of stem-cell treatment for brain-damaged infants. By deliberately restricting blood and oxygen flow to the brains of newborn rats, he and his colleagues simulate the effects of an infant stroke–a devastating event that causes untreatable brain injury in newborn humans.

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Credit: Joseph Yanai

Tagged: Biomedicine, disease, stem cell science, stem cell therapy, adult stem cells, birth defects, neural stem cells

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