Scientists at Case Western Reserve University School of Medicine found a way to rapidly produce pure populations of cells that grow into the protective myelin coating on nerves in mice. Their process opens a door to research and potential treatments for multiple sclerosis, cerebral palsy and other demyelinating diseases afflicting millions of people worldwide.
The findings will be published in the online issue of Nature Methods, Sunday, Sept. 25, at 1 p.m. EST.
"The mouse cells that we utilized, which are pluripotent epiblast stem cells, can make any cell type in body," Paul Tesar, an assistant professor of genetics at Case Western Reserve and senior author of the study, explained. "So our goal was to devise precise methods to specifically turn them into pure populations of myelinating cells, called oligodendrocyte progenitor cells, or OPCs."
Their success holds promise for basic research and beyond.
"The ability of these methods to produce functional cells that restore myelin in diseased mice provides a solid framework for the ability to produce analogous human cells for use in the clinic," said Robert H. Miller, vice dean for research at the school of medicine and an author of the paper.
Tesar worked with CWRU School of Medicine researchers Fadi J. Najm, Shreya Nayak, and Peter C. Scacheri, from the department of genetics; Anita Zaremba, Andrew V. Caprariello and Miller, from the department of neurosciences; and with Eric. C. Freundt, now at the University of Tampa.
Myelin protects nerve axons and provides insulation needed for signals to pass along nerves intact. Loss of the coating results in damage to nerves and diminished signal-carrying capacity, which can be expressed outwardly in symptoms such as loss of coordination and cognitive function.
Scientists believe that manipulating a patient's own OPCs or transplanting OPCs could be a way to restore myelin.
And, they have long known that pluripotent stem cells have the potential to differentiate into OPCs. But, efforts to push stem cells in that direction have resulted in a mix of cell types, unsuitable for studying the developmental process that produces myelin, or to be used in therapies.
Tesar and colleagues are now able to direct mouse stem cells into oligodendrocyte progenitor cells in just 10 days. The team's success relied upon guiding the cells through specific stages that match those that occur during normal embryonic development.
First, stem cells in a petri dish are treated with molecules to direct them to become the most primitive cells in the nervous system. These cells then organize into structures called neural rosettes reminiscent of the developing brain and spinal cord.
To produce OPCs, the neural rosettes are then treated with a defined set of signaling proteins previously known to be important for generation of OPCs in the developing spinal cord.
After this 10 day protocol, the researchers were able to maintain the OPCs in the lab for more than a month by growing them on a specific protein surface called laminin and adding growth factors associated with OPC development.
The OPCs were nearly homogenous and could be multiplied to obtain more than a trillion cells.
The OPCs were treated with thyroid hormone, which is key to regulating the transition of the OPCs to oligodendrocytes. The result was the OPCs stopped proliferating and turned into oligodendrocytes within four days.
Testing on nerves lacking myelin, both on the lab bench and in diseased mouse models, showed the OPCs derived from the process flourished into oligodendrocytes and restored normal myelin within days, demonstrating their potential use in therapeutic transplants.
Because they are able to produce considerable numbers of OPCs – a capability that up until now has been lacking - the researchers have created a platform for discovering modulators of oligodendrocyte differentiation and myelination. This may be useful for developing drugs to turn a patient's own cells into myelinating cells to counter disease.
The National Institutes of Health, CWRU School of Medicine, the New York Stem Cell Foundation, the Myelin Repair Foundation, the National Center for Regenerative Medicine, and the Case Comprehensive Cancer Center funded the research.
Kevin Mayhood | EurekAlert!
Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
16.11.2018 | Health and Medicine
16.11.2018 | Life Sciences
16.11.2018 | Life Sciences