Mice stem cells guided into myelinating cells by the trillions

September 25, 2011, Case Western Reserve University

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 are published in the online issue of , Sunday, Sept. 25.

"The mouse that we utilized, which are pluripotent epiblast , 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 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 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 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 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.

Explore further: Modified adult stem cells may be helpful in spinal cord injury

Related Stories

Modified adult stem cells may be helpful in spinal cord injury

February 24, 2010
Researchers at UTHealth have demonstrated in rats that transplanting genetically modified adult stem cells into an injured spinal cord can help restore the electrical pathways associated with movement. The results are published ...

Movies shed new light on how nerves are wrapped

November 15, 2006
Much like the electrical wiring in your house, the nerves in your body need to be completely covered by a layer of insulation to work properly.

Human ES cells progress slowly in myelin's direction

April 9, 2009
Scientists from the University of Wisconsin, USA, report in the journal Development the successful generation from human embryonic stem cells of a type of cell that can make myelin, a finding that opens up new possibilities ...

Understanding pluripotent stem cells

March 8, 2011
Paul Tesar, PhD, of Case Western Reserve University, a member of the inaugural class of The New York Stem Cell Foundation – Robertson Investigators, published his research on the ability to isolate epiblast stem cells ...

A new program for neural stem cells

May 12, 2011
German researchers succeed in obtaining brain and spinal cord cells from stem cells of the peripheral nervous system.

Novel mouse model of demyelinating disorder

January 14, 2010
In the February 1st issue of G&D, Dr. Brian Popko (The University of Chicago) and colleagues describe how mutation of a gene called ZFP191 leads to disordered CNS myelination in mice -- reminiscent of what is seen in human ...

Recommended for you

Gene plays critical role in noise-induced deafness

October 19, 2018
In experiments using mice, a team of UC San Francisco researchers has discovered a gene that plays an essential role in noise-induced deafness. Remarkably, by administering an experimental chemical—identified in a separate ...

Functional engineered oesophagus could pave way for clinical trials 

October 18, 2018
The world's first functional oesophagus engineered from stem cells has been grown and successfully transplanted into mice, as part of a pioneering new study led by UCL.

New findings cast light on lymphatic system, key player in human health

October 16, 2018
Scientists at the Oklahoma Medical Research Foundation have broken new ground in understanding how the lymphatic system works, potentially opening the door for future therapies.

New model suggests cuffless, non-invasive blood pressure monitoring possible using pulse waves

October 16, 2018
A large team of researchers from several institutions in China and the U.S. has developed a model that suggests it should be possible to create a cuffless, non-invasive blood pressure monitor based on measuring pulse waves. ...

Age-related increase in estrogen may cause common men's hernia

October 16, 2018
An age-related increase in estrogen may be the culprit behind inguinal hernias, a condition common among elderly men that often requires corrective surgery, according to a Northwestern Medicine study was published Oct. 15 ...

Income and wealth affect the mental health of Australians, study shows

October 16, 2018
Australians who have higher incomes and greater wealth are more likely to experience better mental health throughout their lives, new research led by the Bankwest Curtin Economics Centre has found.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Cave_Man
not rated yet Sep 26, 2011
This is a HUGE breakthrough if it can be used with human cells, anyone over 10 years old has mercury amalgam fillings in their mouths which release mercury vapor.

Mercury is extremely detrimental to the myelin sheath of neurons in your brain (explaining the high level of brain diseases and generally retarded behavior)

check out the smoking gun (tooth)
http://www.youtub...nQ-T7oiA

check out what mercury does to your brain
http://www.youtub...=related

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.