Scientists at the Burnham Institute for Medical Research have, for the first time, genetically programmed embryonic stem (ES) cells to become nerve cells when transplanted into the brain, according to a study published today in The Journal of Neuroscience.
The research, an important step toward developing new treatments for stroke, Alzheimer’s, Parkinson’s and other neurological conditions 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 prior attempts at stem cell transplantation.
The team was led 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. Dr. Lipton is also a clinical neurologist who treats patients with these disorders. Collaborators included investigators from The Scripps Research Institute.
“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,” said Dr. Lipton. “These findings could potentially lead to new treatments for stroke and neurodegenerative diseases such as Parkinson’s disease.”
Conditions such as stroke, Alzheimer’s, Parkinson’s and Huntington’s disease destroy brain cells, causing speech and memory loss and other debilitating consequences. In theory, 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. 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.
The work was supported in part by National Institutes of Health (NIH) grants and a Senior Scholar Award in Aging Research from the Ellison Medical Foundation.About Burnham Institute for Medical Research
Josh Baxt | newswise
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences