Researchers at the Burnham Institute for Medical Research in La Jolla, CA have for the first time converted stem cells to nerve cells, and implanted them into mice. The transplantation and accommodation of these cells was successful, and the scientists did not get into the common problems associated with transplanted cells, such as resulting formation of tumors.

Prior to this research, creating pure neuronal cells from ES cells had been problematic as the cells did not always differentiate into neurons. Sometimes they became glial cells, which lack many of the neurons’ desirable properties. Even when the neuronal cells were created successfully, they often died in the brain following transplant—a process called programmed cell death or apoptosis. In addition, the cells would sometimes become tumors.
Dr. Lipton solved these problems 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. Using MEF2C, the researchers created 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,” said Dr. Lipton. “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.”
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. Performing intricate electrical studies, Dr. Lipton’s investigative team showed that the new nerve cells, derived from the stem cells, could send and receive proper electrical signals to the rest of the brain. They then determined if the new cells could provide cognitive benefits to the stroke-afflicted mice. The team executed a battery of neurobehavioral tests and found that the mice that received the transplants showed significant behavioral 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.

Press release: Nerve Cells Derived from Embryonic Stem Cells and Transplanted into Mice May Lead to Improved Brain Treatments …
Image credit: Wellcome images: Dorsal Root Ganglion neurones in culture…

A group at Stony Brook University has modified the polio virus to create a weakened version, which, when injected, went on to effectively immunize lab mice. The team of molecular biologists and computer scientists used a novel algorithm to sort through potential recordings of the genome that would produce the desired proteins. The technique may lead to practical, systematic methods of developing future viral vaccines.

Because of the redundancy of the genetic code, there are an unimaginably large number of ways to encode any given protein. For poliovirus proteins, there are more possible encodings (10 to the 442 power) than atoms in the universe. Using a powerful computer algorithm, the team found particular re-codings of the genome predicted to weaken the virus.
The researchers made hundreds of small mutations in the genome that perfectly preserved the viral proteins but changed the way those proteins were encoded by RNA (ribonucleic acid), so that pairs of amino acids were added by transfer RNAs (tRNAs) that rarely work together in normal proteins. They call the process “Synthetic Attenuated Virus Engineering,” or “SAVE.” The resulting virus contains completely authentic, wild-type poliovirus proteins. However, each of the hundreds of mutations causes a tiny defect by creating an obstacle – a genetic “speed bump” – in translating the genetic code into a protein.
“Translation of this unusual genome into viral proteins was inefficient, and the most highly re-coded virus was weakened to the point where it was unable to infect cells,” says J. Robert Coleman, Lead Author and a graduate student in Molecular Genetics and Microbiology.
The reduced translational efficiency of these chimeric viruses reduced their ability to cause disease. The team injected mice with the re-coded polioviruses. Most mice showed no signs of disease but did produce anti-polio antibodies. These mice were then immune against infection by the normal, fully virulent poliovirus.

Press release: SBU Team Designs Customized “Wimpy” Polioviruses, A Method That Could Be A New Path To Vaccines …
Abstract in Science: Virus Attenuation by Genome-Scale Changes in Codon Pair Bias
Image: The structural appearance of Poliovirus (type I, Mahoney strain) coating protein