RxPG News Feed for RxPG News

Medical Research Health Special Topics World
  Home
 
   Health
 Aging
 Asian Health
 Events
 Fitness
 Food & Nutrition
 Happiness
 Men's Health
 Mental Health
 Occupational Health
 Parenting
 Public Health
 Sleep Hygiene
 Women's Health
 
   Healthcare
 Africa
 Australia
 Canada Healthcare
 China Healthcare
 India Healthcare
 New Zealand
 South Africa
 UK
 USA
 World Healthcare
 
   Latest Research
 Aging
 Alternative Medicine
 Anaethesia
 Biochemistry
 Biotechnology
 Cancer
 Cardiology
 Clinical Trials
 Cytology
 Dental
 Dermatology
 Embryology
 Endocrinology
 ENT
 Environment
 Epidemiology
 Gastroenterology
 Genetics
 Gynaecology
 Haematology
 Immunology
 Infectious Diseases
 Medicine
 Metabolism
 Microbiology
 Musculoskeletal
 Nephrology
 Neurosciences
  Brain Diseases
  Demyelinating Diseases
  Headache
  Memory
  Neurochemistry
  Neurodegenerative Diseases
  Regeneration
  Spinal Cord Diseases
  Stroke
  Taste
  Trigeminal Neuralgia
 Obstetrics
 Ophthalmology
 Orthopedics
 Paediatrics
 Pathology
 Pharmacology
 Physiology
 Physiotherapy
 Psychiatry
 Radiology
 Rheumatology
 Sports Medicine
 Surgery
 Toxicology
 Urology
 
   Medical News
 Awards & Prizes
 Epidemics
 Launch
 Opinion
 Professionals
 
   Special Topics
 Ethics
 Euthanasia
 Evolution
 Feature
 Odd Medical News
 Climate

Last Updated: Oct 11, 2012 - 10:22:56 PM
Regeneration Channel

subscribe to Regeneration newsletter
Latest Research : Neurosciences : Regeneration

   EMAIL   |   PRINT
Using Embryonic Stem Cells to Awaken Latent Motor Nerve Repair

Jul 1, 2006 - 5:23:00 PM , Reviewed by: Priya Saxena
“Paralysis is like turning on a light switch and the light doesn’t go on. The connectivity is messed up but you don’t know where. We’ve asked stem cells to go where needed to fix the circuit.”

 
[RxPG] In a dramatic display of stem cells’ potential for healing, a team of Johns Hopkins scientists reports that they’ve engineered new, completed, fully-working motor neuron circuits -- neurons stretching from spinal cord to target muscles -- in paralyzed adult animals.

The research, in which mouse embryonic stem (ES) cells were injected into rats whose virus-damaged spinal cords model nerve disease, shows that such cells can be made to re-trace complex pathways of nerve development long shut off in adult mammals, the researchers say.

“This is proof of the principle that we can recapture what happens in early stages of motor neuron development and use that to repair damaged nervous systems,” says Douglas Kerr, M.D., Ph.D., a neurologist who led the Hopkins team.

“It’s a remarkable advance that can help us understand how stem cells can begin to fulfill their great promise,” says Elias A. Zerhouni, director of the National Institutes of Health. “Demonstrating restoration of function is an important step forward, though we still have a great distance to go.”

The researchers created what amounts to a cookbook recipe to restore lost nerve function, Kerr explains. The approach could one day repair damage from such diseases as ALS (Lou Gehrig’s disease), multiple sclerosis or transverse myelitis or from traumatic spinal cord injury, the researchers say. “With small adjustments keyed to differences in nervous system targets,” Kerr says, “the approach may also apply to patients with Parkinson's or Huntington’s disease.”

In a report on the study, to be released online June 26 in the Annals of Neurology, the Hopkins team says 11 of the 15 treated rats gained significant, though partial, recovery from paralysis after losing motor neurons to an aggressive infection with Sindbis virus -- one that, in rodents, specifically targets motor neurons and kills them. The animals recovered enough muscle strength to bear weight and step with the previously paralyzed hind leg.

Kerr likens the approach to electrical repair. “Paralysis is like turning on a light switch and the light doesn’t go on. The connectivity is messed up but you don’t know where. We’ve asked stem cells to go where needed to fix the circuit.”

For a brief period after a nerve dies, it leaves behind what’s essentially an empty shell, with some scaffolding and non-nerve substances remaining. But with ES injections at the right time and place, and by adding the right cues, we’ve learned to restore the biological ‘memory’ for growing neurons, which is clearly still in place,” he added.

The motor circuit engineering combines recent discoveries on stem cell differentiation, a growing understanding of early development of the nervous system, and insights into behavior of the nervous system in traumatic injury, Kerr notes.

“As adults, our cells no longer respond to early developmental cues because those cues are usually gone,” says Kerr. “That’s why we don’t recover well from severe injuries. But that’s what we believe we have changed. We asked what was there when motor neurons were born, and specifically what let motor neurons extend outward. Then we tried to bring that environment back, in the presence of adaptable, receptive stem cells.”

In the study, Kerr’s team first pre-treated cultures of mouse embryonic stem cells with growth factors that both increase survival and prompt specialization into motor neurons. Adding retinoic acid and sonic hedgehog protein -- agents that direct cells in the first weeks of life to assume the proper places in the spinal cord -- readied the conditioned ES cells for the motor neuron circuit that starts in the spinal cord. Then, stem cells were fed into the paralyzed rats’ spinal cords.

Extending new motor neurons in an adult nervous system, however, meant overcoming hurdles. One involved myelin, the fatty material that insulates mature motor neurons. Like the coating on electrical wire, myelin prevents weakening of the traveling electrical impulse and lets it continue long distances. In humans, the myelinated sciatic nerve, for example, exits the spinal cord and extends to the leg muscles it activates, carrying impulses several feet.

Once laid down, however, myelin inhibits further nerve growth -- nature’s way to discourage excessive wiring in the nervous system. “We had to overcome inhibition from myelin lingering in the dead nerve pathways,” Kerr explains. Two recently-developed agents, rolipram and dbcAMP enabled that.

The assorted treatments let the new motor neurons survive, grow through the spinal cord and extend slightly into the outlying nervous system. A second hurdle remained in getting the neurons to skeletal muscle targets.

As suggested by earlier work by team member Ahmet Hoke on repair in the outlying, peripheral nervous system, the researchers applied GDNF, a powerful stimulator of neuron growth, to the remains of the newly-dead sciatic nerve at a point near its former leg muscle contacts. GDNF attracted the extending motor neurons, “luring” them to the muscles. To ensure a continuous supply of GDNF, the researchers relied on injected fetal mouse neural stem cells, a known source of the molecule.

Of some 4,100 new motor neurons created in the spinal cord, roughly 200 exited the cord and 120 reached skeletal muscle, forming typical nerve-muscle junctions, with appropriate, typical chemical markers. Microscopically, the neurons and their muscle associations appear identical to natural ones in healthy animals.

Fifty of the new neurons were found to carry electrical impulses. (Because such testing is time and labor intensive, only a small area of leg muscle was assayed. The improved ability of treated rats, however, suggests more functional neurons are likely.) The rats gained weight, were more mobile in their cages and measures of muscle strength increased.

Animals treated without even one component of the “cocktail” experienced no such recovery. Novel ways of tracing the neurons back to their source assured the scientists that they indeed had come from the injected stem cells, not from lingering host neurons.



Publication: June 26 in the Annals of Neurology
On the web: www.hopkinsmedicine.org 

Advertise in this space for $10 per month. Contact us today.


Related Regeneration News
Salamanders can regenerate damaged lungs
Severed nerve fibers in spinal cord can regenerate for long distances
Common brain cells may have stem-cell-like potential
Using Embryonic Stem Cells to Awaken Latent Motor Nerve Repair
Understanding how axons find their destinations
Novel stem cell technology leads to better spinal cord repair
Myosin-II: A new focus for the mechanism of nerve growth
Structural remodeling of neurons demonstrated in mature brains
How "baby" neurons are integrated into brain
Nerve regeneration is possible in spinal cord injuries

Subscribe to Regeneration Newsletter

Enter your email address:


 Additional information about the news article
Research begins this summer to see how well the technique applies to human nerve recovery, using federally-approved human ES cells in larger mammals like pigs, Kerr says. Each of six academic institutions in a new collaboration will tackle a different major question of safety and effectiveness. Questions of tumor-formation, often a concern with ES cells, of the safety of surgery and of the ES cells’ ability to form healthy motor circuits are major questions to answer. Several years of testing and thorough data evaluation would occur before applying to the FDA to approve human clinical trials. The study was supported by Families of SMA, Andrew’s Buddies/Fight SMA, the ALS Association and The Robert Packard Center for ALS Research at Johns Hopkins, the Muscular Dystrophy Association, Wings Over Wall Street, and a grant from the NIH.

Kerr is a grantee of The Packard Center for ALS Research at Johns Hopkins. He also directs Project RESTORE, a Hopkins-based undertaking to advance therapies for transverse myelitis and multiple sclerosis.

Others on the research team from the Department of Neurology at the Johns Hopkins University School of Medicine include Jeffrey Rothstein, M.D., Ph.D.; Ahmet Hoke, M.D., Ph.D.; Nicholas Maragakis, M.D.; Yun Sook Kim, Ph.D.; Sonny Dike, M.D.; Deepa Deshpande, M.S.; Chitra Krishnan, M.S., and Jennifer Drummond. Researchers from the Department of Molecular Microbiology and Immunology at the Johns Hopkins University Bloomberg School of Public Health include Jessica Carmen, Tara Martinez and Irina Shats. Jeremy Shefner, M.D., Ph.D., of the Department of Neurology at the State University of New York Upstate Medical University, Syracuse, N.Y., also contributed to the study.
 Feedback
For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 
Contact us

RxPG Online

Nerve

 

    Full Text RSS

© All rights reserved by RxPG Medical Solutions Private Limited (India)