Stem cell breakthrough may pave way for new brain treatments

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Washington, June 25 : In a first of its kind study, scientists at the Burnham Institute for Medical Research have genetically programmed embryonic stem (ES) cells to become nerve cells when transplanted into the brain.

Headed by Stuart A. Lipton, M.D., Ph.D., professor and director of the Del E. Webb Neuroscience, Aging, and Stem Cell Research Center at Burnham, the study has paved the way for developing new treatments for stroke, Alzheimer's, Parkinson's and other neurological conditions.

The researchers showed that mice afflicted by stroke showed tangible therapeutic improvement following transplantation of these cells. None of the mice formed tumors, which had been a major setback in earlier attempts at stem cell transplantation.

"We found that we could create new nerve cells from stem cells, transplant them effectively and make a positive difference in the behavior of the mice. These findings could potentially lead to new treatments for stroke and neurodegenerative diseases such as Parkinson's disease," said Lipton.

Conditions such as stroke, Alzheimer's, Parkinson's and Huntington's disease destroy brain cells, causing speech and memory loss and other debilitating consequences. It is believed that transplanting neuronal brain cells could restore at least some brain function, just as heart transplants restore blood flow.

Prior to this research, creating pure neuronal cells from ES cells had been problematic as the cells did not always differentiate into neurons. Lipton and his team found a solution to this problem by inducing ES cells to express a protein, discovered in his laboratory called myocyte enhancer factor 2C (MEF2C). MEF2C is a transcription factor that turns on specific genes which then drive stem cells to become nerve cells.

They used MEF2C to create colonies of pure neuronal progenitor cells, a stage of development that occurs before becoming a nerve cell, with no tumors. These cells were then transplanted into the brain and later became adult nerve cells. MEF2C also protected the cells from apoptosis once inside the brain.

"To move forward with stem cell-based therapies, we need to have a reliable source of nerve cells that can be easily grown, differentiate in the way that we want them to and remain viable after transplantation. MEF2C helps this process first by turning on the genes that, when expressed, make stem cells into nerve cells. It then turns on other genes that keep those new nerve cells from dying. As a result, we were able to produce neuronal progenitor cells that differentiate into a virtually pure population of neurons and survive inside the brain," said Lipton.

The next step was to determine whether the transplanted neural progenitor cells became nerve cells that integrated into the existing network of nerve cells in the brain.

The researchers carried out intricate electrical studies and showed that the new nerve cells, derived from the stem cells, could send and receive proper electrical signals to the rest of the brain. For determining if the new cells could provide cognitive benefits to the stroke-afflicted mice, they executed a battery of neurobehavioral tests and found that the mice that received the transplants showed significant behavioural improvements, although their performance did not reach that of the non-stroke control mice.

These results suggest that MEF2C expression in the transplanted cells was a significant factor in reducing the stroke-induced deficits.

The study is published in The Journal of Neuroscience.

ANI

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