Wednesday, March 29, 2006

Spinal Cord Injury Reduced With Cells Transplanted From Adult Mice Brain Cells

Scientists at Toronto University and the Toronto Western Research Institute of Canada managed to reduce some of the paralysis of rats with spinal cord injury with cells transplanted from adult mice brain cells. This could eventually lead to treatment for humans with paralysis as a result of spinal cord injury.

If cells from the paralyzed human patient could be transplanted, we may eventually have an effective treatment. Dr. Michael Fehlings, lead researcher, said even some cells in the spinal cord itself could be used (rather than brain cells).

You can read about this research in the Journal of Neuroscience.

The scientists worked on 97 rats with spinal cord injuries. Brain cells from adult mice were implanted into the spinal cords of the rats at two and eight weeks after injury. The rats that received the brain cells two weeks after injury gained coordination on their hind legs and started to develop the ability to bear weight (on their back legs) - they did not start walking normally.

The rats that received the brain cells eight weeks after injury experienced no improvement in their paralysis. If this research eventually evolves into some kind of human treatment, it will have to be carried out soon after injury to the spinal cord.

Unlike previous experiments which managed to ease paralysis in laboratory animals, this research managed to do it with adult brain cells, rather than embryonic stem cells (or cells from fetuses). These adult brain cells, neural precursor cells, can only evolve into cells of the nervous system. Embryonic stem cells can turn into any kind of cell.

These adult mice brain cells, when implanted into the spinal cord, create a sheath (kind of insulation) around the nerve fibres - very much like the plastic insulation you find around electric cables in your home. People (and animals) with spinal cord injuries have defective sheaths (or areas where there is no insulation at all). By restoring the insulation, paralysis is eased (the person can started moving again).

By: Christian Nordqvist
Editor: Medical News Today
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Wednesday, March 22, 2006

Study Finds Nerve Regeneration Possible in Spinal Cord Injuries

Spinal Cord Injury Recovery

A team of scientists at UCSF has made a critical discovery that may help in the development of techniques to promote functional recovery after a spinal cord injury.

By stimulating nerve cells in laboratory rats at the time of the injury and then again one week later, the scientists were able to increase the growth capacity of nerve cells and to sustain that capacity. Both factors are critical for nerve regeneration.

The study, reported in the Nov. 15 issue of the Proceedings of the National Academy of Sciences, builds on earlier findings in which the researchers were able to induce cell growth by manipulating the nervous system before a spinal cord injury, but not after.

Key to the research is an important difference in the properties of the nerve fibers of the central nervous system (CNS), which consists of the brain and spinal cord, and those of the peripheral nervous system (PNS), which is the network of nerve fibers that extends throughout the body.

Nerve cells normally grow when they are young and stop when they are mature. When an injury occurs in CNS cells, the cells are unable to regenerate on their own. In PNS cells, however, an injury can stimulate the cells to regrow. PNS nerve regeneration makes it possible for severed limbs to be surgically reattached to the body and continue to grow and regain function.

Regeneration occurs because PNS cell bodies are sensitive to damage to their nerve processes, and they react by sending out a signal that triggers the nerve fibers to regrow, explains Allan Basbaum, senior study author and chair of the UCSF Department of Anatomy. "Apparently this communication doesn't take place within the CNS."

Scientists do not yet know the biochemical cause for the difference, he adds.

The traditional scientific approach in efforts to enhance CNS regeneration is to manipulate the biochemical environment of the cells at the site of the spinal cord injury, according to Basbaum. Instead of this type of investigation, Basbaum's team used nervous system manipulation techniques to apply the principles of PNS cell growth capability to CNS cells.

The researchers took advantage of an unusual class of nerve fibers that has both a PNS and a CNS branch. Previously, the researchers had shown in animal studies that an injury made to the peripheral branch prior to a spinal cord injury provided the essential communication signal that enabled the CNS branch to grow. But this only worked if the PNS injury - which served as priming for CNS cell growth - was made at least a week before the CNS injury.

"Clearly this would have no utility in clinical situations, where treatments cannot be made in anticipation of spinal cord injury," says Basbaum. Another challenge the researchers faced was stimulating CNS cells to grow beyond the injury site and into healthy tissue, which is essential to help regain function.

"A PNS injury at the time of spinal cord damage will only promote growth of nerve fibers into the spinal cord lesion, but not into the tissue beyond it. This is because growth capacity is enhanced, but it is not sustained," he explains. In the new study, researchers evaluated the effect of two peripheral nerve lesions (injuries) in animals with spinal cord injury. One lesion was made at the time of the cord injury and a second was made a week later. Both lesions were located in the animals' sciatic nerve, which is part of the PNS.

The researchers found that the two "priming lesions" not only promoted significant spinal cord regeneration within the area of the spinal cord injury, but more important, the regenerating axons grew back into normal areas of the spinal cord, where the hope is that functional connections can be reestablished. Axons are the long, fragile, fibers that conduct impulses between nerve cells in the brain, spinal cord and limbs.

"Getting the growth beyond the lesion is key. If we can get those axons to grow even a few centimeters past the lesion, they can start sending signals and developing new circuits throughout the body," says Basbaum.

Basbaum adds that timing is critical for successful nerve regeneration. "There is a window of opportunity just after the injury when the potential for growth through and beyond the lesion is greatest. If we wait too long after an injury, the cells revert back to their normal, no-growth state. Plus, scar tissue begins to form, making growth difficult."

"These findings give us hope. The nervous system is capable of being modified to a level where we can achieve nerve fiber growth. Ultimately, the goal is to promote growth and sustain it long enough for recovery of movement to occur in spinal cord injury patients," he concludes.
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Monday, March 20, 2006

Stretching the Limits to Heal Spinal Cords

For years, scientists have been trying to make injured spinal cords grow back, with limited success.

Lying awake in bed one night, neurobiologist Douglas H. Smith came up with an offbeat alternative:

Instead of trying to regrow the damaged nerves, how about taking nerve cells from elsewhere in the body and getting them to stretch? After all, he reasoned, a similar process must be going on when whales and giraffes grow their spinal cords to tremendous lengths.

So far, it's working. Smith and his University of Pennsylvania colleagues have taken clumps of nonessential nerve-cell bodies from rats, stretched them very slowly - a millimeter or two a day, in specially constructed stretching boxes - and successfully implanted them into other rats with injured spinal cords.

Still to come are tests to show if the implanted nerves actually "work." Any trials on humans are years away.

But the research is seen as promising, and is just one of several dramatic recent advances in science's quest to reverse the irreversible.

Some scientists are using drugs to limit the harmful inflammation and other secondary damage that arises within hours of a spinal injury. Others, including Drexel University's prominent spinal-cord group, have restored some muscular function in lab animals by using neural stem cells.

Still others are using drugs to stimulate neural regrowth. A variety of clinical trials are under way or about to begin.

The breadth of activity reflects what some see as a coming of age of spinal-cord science. It has been helped along by a shift in federal spending priorities and an increase in private funds - attributed in part to the lobbying efforts of the late actor Christopher Reeve and his wife, Dana, who died earlier this month.

"I think we have a lot more hope for clinical research into whether some of the things in labs are going to have an impact on patients," says Phillip Popovich, a spinal-cord researcher at the Ohio State University College of Medicine.

Partial recovery

Scientists caution against raising the hopes of those with spinal-cord injuries, of whom there are an estimated 250,000 in the United States, according to the University of Alabama, Birmingham.

There are no immediate expectations that paralyzed people will walk again, and researchers say that right now, that isn't even the primary goal.

In surveys, many patients suffering from spinal-cord injury say they become used to living in their wheelchairs, and are more interested - at first - in smaller advances that can make them independent. Among these are regaining bladder or bowel control or partial movement in paralyzed limbs.

"Seemingly small things can make such an incredible difference in quality of life," says Oswald Steward, director of the Reeve-Irvine Research Center at the University of California in Irvine.

Lately, scientists at the Reeve Center, named for the late actor, have used neural stem cells to replenish the myelin sheaths around damaged spinal nerves in laboratory rats. That process - akin to replacing the insulation on electrical wire - enabled the rats to get back some mobility.

At Drexel's College of Medicine, scientists have transplanted another type of neural stem cell into the spinal cords of injured rats, resulting in the partial restoration of bladder control.

The cells did not replace the damaged circuits, says Drexel's Itzhak Fischer, chair of the school's Department of Neurobiology and Anatomy. Rather, they seem to have encouraged compensatory "sprouting" in adjacent, uninjured cells.

But demonstrating a technique in rats is one thing. In people it's quite another.

Rats are hardy, resilient animals, with redundant capability built into their nervous systems. After technicians in Smith's Penn lab cut out centimeter-long notches from rodents' spinal cords, for example, the animals could still walk.

Yet the initial experiments have shown promise, Smith and his co-authors reported in the January issue of the journal Tissue Engineering.

When stretched to the right length and implanted into the injured spinal cords, the replacement nerves - nicknamed "jumper cables" - took hold.

Four weeks after implantation, the new nerves not only survived, but grew into the damaged spinal cords.

A true test will involve transmitting electrical signals along the length of repaired spinal cords. That research is scheduled to begin during the coming year.

Stretching nerves

Smith, 46, the boyish director of Penn's Center for Brain Injury and Repair, got the idea one night while thinking about the harmful stretching of brain cells that occurs in a concussion.

Could stretching be adapted to repair spinal cords? he wondered.

A review of the literature revealed almost no research into how spinal cords grow.

Which is when he decided to grow them himself.

The lab started by extracting the cell bodies from rats' peripheral nerves - the conduits that relay sensory information from the legs and other body parts back to the spinal cord.

Researchers then placed clumps of nerve-cell bodies onto two adjacent plastic membranes, each coated with jelly-like collagen. The cells were then immersed in a soup of liquid nutrients.

Tiny branches - the beginnings of the nerve fibers known as axons - soon sprouted from the cells until the adjacent membranes were connected.

Then, slowly and steadily with the use of computers, the two membranes were pulled apart. The pulling takes place in little boxes that might call to mind a torture instrument.

"Torquemada would be proud," Smith quips, referring to the Spanish Inquisition's grand inquisitor.

But contrary to the experience of torture victims, the nerves seem to like the stretching just fine. They absorb nutrients from the surrounding growth medium and grow thicker even as they are pulled.

Smith thinks the process is not much different from what occurs in the growth of a real spinal cord.

"We're just kind of copying that from nature," he says, adding that his approach could be used in conjunction with other techniques, such as stem cells.

Drexel's Fischer, who was not involved in the stretching research, calls it "an engineering triumph."

If tests show that stretched nerves are truly functional after implantation, human trials could begin soon after.

Smith, like most in his field, is wary of making predictions, given that bold statements have backfired before. In the 1980s, for example, one prominent researcher is said to have predicted that the problem of spinal-cord injury would be solved within a decade.

Yet Steward, the Reeve-Irvine Center director, understands the need to hope, citing his experience with the actor.

At one point during the course of lobbying for more research funds, Reeve was optimistic that stem cells would benefit him personally, Steward says. Eventually, the actor told Steward, he realized he would not live long enough.

"He certainly realized that what he was doing was for later," Steward says. "But did he hope? You bet."

By TOM AVRIL - Philadelphia Inquirer
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Saturday, March 11, 2006

University Reports Successful Stem-Cell Experiment

Spokesman Says Nerve Repair Takes Major Step

The University of Louisville is reporting a second successful experiment in its stem-cell research.

A spokesman said it's a major step in nerve repair that offers hope for treating an array of disorders, television station WLKY reported.

A rat with a spinal-cord injury was able to move normally just weeks after an injection containing adult stem cells from a human nose.

The nose cells were transformed into nerve cells.

Scientists said they hope the research on rats will lead to treatments for spinal cord injuries, multiple sclerosis, Parkinson's disease and other nerve disorders.
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Friday, March 03, 2006

Finding May Lead to New Therapy for Nervous System Disorders

Stem cells obtained from adult nasal passages can be transformed into nerve cells that restore mobility and function to rats with spinal cord injuries, a University of Louisville study has shown.

Researchers have stimulated these cells to become neurons, interact with muscles and make dopamine, a chemical that helps carry electrical signals within the nervous system, said Fred Roisen, a neuroscientist who led the research.

Results of the study were reported today in the journal Stem Cells.

The discovery is significant because it could lead to a new way to use a person?s own cells to treat spinal cord injury, multiple sclerosis, Parkinson?s disease and other nerve disorders, Roisen said.

In the study, researchers took stem cells from adults undergoing elective nasal sinus surgery and used certain compounds to coax the cells into becoming neurons that attached to muscle tissue under laboratory conditions. The team also has shown that the newly-created cells can produce myelin, a protective coating that insulates the nervous system much like the coating on an electrical cord.

"We are extremely enthusiastic about these results," Roisen said. "They show that it may be possible in the future to take stem cells from a person's nose and use them to regenerate damaged nerve tissue in the same person."

Since patients undergoing that procedure would receive their own cells, they would not need to take anti-rejection drugs and could avoid other complications often associated with using cell-based treatments for disease, he added.
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Effective Treatment For Spinal Cord Injury Can Vary - March 3, 2006

Los Angeles, California (AHN) - According to a new study published in the February 28, 2006, issue of Neurology, the scientific journal of the American Academy of Neurology, body weight-supported treadmill training is not more effective than conventional mobility rehabilitation for restoring movement to those with partial spinal cord injury. The study showed an unexpectedly high number of patients achieved functional walking speeds regardless of treatment type.

The multi-center trial analyzed 117 individuals who had a partial spinal cord injury within the previous eight weeks. All patients received an equal amount of therapy for 12 weeks.

Study author Bruce H. Dobkin, MD, of Reed Neurologic Research Center at the University of California, Los Angeles says, "We initially expected that body weight-supported treadmill training would be more effective to regain walking ability...But what we found was no significant difference in strategies among individuals...who achieved walking abilities beyond expectations."

Dobkin says, given that both therapy methods produced similar outcomes, clinicians and patients could base their use of each strategy on personal preferences, skill, availability of equipment, and costs."

Andrea Moore - All Headline News Staff Reporter
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