Laboratory-grown human neural stem cells, the building blocks of the brain, were successfully transplanted for the first time into the brains of aged rats and dramatically improved the animals' cognitive function, according to a study by University of Illinois at Chicago researchers.
Researchers led by Kiminobu Sugaya, an assistant professor of psychiatry at UIC, found that in a spatial memory task, aged rats that had received the transplants were able to perform as well as younger rats without memory impairments. The findings are reported in the May 1 edition of NeuroReport, a fully refereed online journal that offers fast publication times for breaking scientific news. The journal is devoting a special issue to this paper.
The research is a first step in Sugaya's hope of curing neurodegenerative diseases in humans by replacing overworked brain cells with fresh cultured stem cells. The transplantation of stem cells, followed by incorporation of the cells into the host brain and subsequent cognitive improvement, is the first successful experiment of its kind in the world. The results of the study could lay the foundation for new treatments in diseases such as Alzheimer's and Parkinson's.
Neural cell transplant studies recently suffered a setback when transplanted fetal cells worsened symptoms in Parkinson's patients. However, Sugaya pointed out, his team injected different types of cells into the brain-not already differentiated neural fetal cells but laboratory-grown stem cells, which are not differentiated.
This tactic allowed the host brain to take over, dictating where the stem cells should migrate and what types of cells they should become. As a result, Sugaya said, the transplanted cells became functionally integrated into the neuronal circuitry of the host animal.
"We believe this offers a promising line of research in treating brain disorders," said Sugaya.
In the study, 32 rats were trained to swim to a hidden escape platform in a standard water maze. In trials four months later, the researchers timed the rats to assess how well they had learned the task and how quickly they recalled the location of the platform. Aged, memory-impaired rats that had received the implants performed as well as-and in one case, better than-younger rats. The aged rats also outperformed control animals.
Postmortem examination of the rats' brains demonstrated that the transplanted human brain cells had not only differentiated and were thriving in the new environment, but that the rats' own neuronal fibers had grown dramatically in areas associated with spatial memory.
Sugaya theorizes that the transplanted stem cells may have replaced or augmented the function of old or damaged neural cells in the rats' brains. Alternatively, or in addition, he said, the stem cells may have secreted a protective substance that improved the function of the rats' existing brain circuitry.
"The transplanted stem cells may have helped both directly and indirectly," Sugaya said.
The researchers crossed a major technical hurdle in their transplantation work.
"Previous studies have failed to produce working brain cells from transplants of stem cells," said Sugaya. "In our case, the stem cells were clearly incorporated into the wiring of the host brain."
Co-authors on the study, all of UIC, are postdoctoral researcher Tingyu Qu, graduate student Christopher Brannen, and medical student Hojoong Kim. Funding for the study was provided by the UIC department of psychiatry.
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