Stem Cell Research
Human Brain Cells Grown Inside Mouse Skull
Dec 13, 2005 - 3:28:38 PM

Previous studies have shown that undifferentiated human embryonic stem cells (hESC) can survive in the brains of laboratory rats with Parkinson’s disease. But until now it was unclear whether hESCs can become fully functional members of the host animal’s neuronal architecture - a basic necessity if stem cells are ever to be used in medical treatments replenishing missing or damaged neurons in human patients with neurodegenerative diseases such as Parkinson's or Alzheimer’s disease.

Now, research at the Salk Institute for Biological Studies indicates for the first time that hESCs mature into fully functional adult brain cells and integrate into the existing nervous system when these human cells are injected in the developing brains of two-week-old mouse embryos.

The Salk researchers led by Fred H. Gage, Ph.D, professor and co-head of the Laboratory of Genetics at the Salk Institute, published their finding in this week’s Proceedings of the National Academy of Science.

“Besides its therapeutic potential, our finding also opens up the possibility to study human disease in a new context,” says first author Alysson R. Muotri, Ph.D. “We can ask if neurodegeneration is the function of an individual diseased cell or if it is caused by the local environment in the brain.”

Far less than 0.1 percent of their brain cells were of human origin, and those few had taken on the size and shape of their neighbors. “This illustrate that injecting human stem cells into mouse brains doesn’t restructure the brain,” explains Gage.

At least in theory, hESCs can grow indefinitely in the lab as unspecialized cells and can be coaxed to differentiate into various cell types.

“This assay will be very valuable to determine whether any given human stem cell lines still have the capacity to form fully functional neurons,” says Gage, explaining that scientists currently do not know whether stem cells that have been kept in culture outside the body for extended periods of time have lost the potential to become a neuron or not.

He also emphasizes that “this procedure will also allow other laboratories and drug companies to test the toxicity of new compounds and assess their effects on human brain cells, not just in a Petri dish, but in the context of a functional brain.”

In the past, hESC injected into adult mice often formed tumors or were rejected by the mouse immune system. Hoping to circumvent these problems, Gage and his team opted for injecting hESCs into the developing brains of embryonic mice.

The green glowing hESCs differentiated into different types of neurons and supporting glia cells, migrated throughout the brain and settled in different regions without forming tumors or being rejected by the mouse’s immune system.

“When we characterized these cells two months later, we found that had the morphology, shape and characteristics of mouse cells,” says Gage.

Other authors who contributed to the work include co-first author Kinichi Nakashima, formerly at the Salk and now at Nara Institute of Science and Technology in Japan, and post-doctoral researchers Nicolas Toni and Vladislav M. Sandler. In accordance with guidelines and the Salk’s internal Human Stem Cell Research Guidelines, the mice used in these experiments were not allowed to breed.

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