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Human brain cells can develop in mice - 13-12-2005, 12:44 AM

LOS ANGELES, Dec. 12 (Xinhuanet)-- Human embryonic stem cells injected into the brains of fetal mice can develop into functioning adult brain cells, a US research team reported on Monday.


This finding not only marks a breakthrough in embryonic stem cell research, but also provides a much needed animal model for studying human brain development and disease, such as the Parkinson's and the Alzheimer's, said the researchers led by Fred Gage at The Salk Institute for Biological Studies, California.

The team reported its achievement in the latest issue of the Proceedings of National Academy of Sciences.

Although previous studies have shown that human embryonic stem cells implanted into mouse brain can develop into adult brain cells, it was unclear if these cells were functional. Also, the human cells often formed tumors or were rejected by the mouse immune system.

To improve upon these earlier attempts, the researchers injected human embryonic stem cells into the brains of fetal mice and found that the cells developed into neurons, as well as glia or support cells, without tumor formation or immune rejection.

Some 100,000 human embryonic stem cells per mouse were injected into the brains of 14-day-old rodent embryos. Those mice were eachborn with about 0.1 percent of human cells, the researchers said.

Two months after transplantation, human stem cells had migrated throughout the mice brain and incorporated into a variety of brain regions, according to the researchers.

They found the human neuron cells had normal electrical activity 18 months after transplantation, indicating that they had developed into fully functional adult brain cells.

"Our results show that human embryonic stem cells implanted in the brain ventricles of embryonic mice can differentiate into functional neural lineages and generate mature, active human neurons that successfully integrate into the adult mouse forebrain," their paper said.

"Moreover, this study reveals the conservation and recognition of common signals for neural differentiation throughout mammalian evolution. The chimeric model will permit the study of human neural development in a live environment, paving the way for the generation of new models of human neuro degenerative and psychiatric diseases," they added.

In addition, mice containing human brain cells could potentially speed up the screening process for therapeutic drugs, the researchers suggested, while trying to clear up the concerns of breeding "human-mice."

"Genetic manipulation of human embryonic stem cells (by recombination or delivery of small interfering RNA) or somatic nuclear transfer will allow the generation of a large spectrum of modified donor-derived precursor cells that can then be assayed invivo in a wild-type or mutant recipient brain, producing a mouse-human chimeric nervous system."
"Such a strategy might allow the direct examination of the effect of potential therapeutic molecules on human stem cells in alive and functioning nervous system, even in long-term paradigms,"they said. Enditem


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