Stem Cells Identified for Spinal-Cord Repair

A researcher at MIT?s Picower Institute for Learning and Memory has pinpointed stem cells within the spinal cord that, if persuaded to differentiate into more healing cells and fewer scarring cells following an injury, may lead to a new, non-surgical treatment for debilitating spinal-cord injuries.

The work, reported in the July issue of the journal PLoS (Public Library of Science) Biology, is by Konstantinos Meletis, a postdoctoral fellow at the Picower Institute, and colleagues at the Karolinska Institute in Sweden. Their results could lead to drugs that might restore some degree of mobility to the 30,000 people worldwide afflicted each year with spinal-cord injuries.

In a developing embryo, stem cells differentiate into all the specialized tissues of the body. In adults, stem cells act as a repair system, replenishing specialized cells, but also maintaining the normal turnover of regenerative organs such as blood, skin or intestinal tissues.

The tiny number of stem cells in the adult spinal cord proliferate slowly or rarely, and fail to promote regeneration on their own. But recent experiments show that these same cells, grown in the lab and returned to the injury site, can restore some function in paralyzed rodents and primates.

The researchers at MIT and the Karolinska Institute found that neural stem cells in the adult spinal cord are limited to a layer of cube- or column-shaped, cilia-covered cells called ependymal cells. These cells make up the thin membrane lining the inner-brain ventricles and the connecting central column of the spinal cord.

?We have been able to genetically mark this neural stem cell population and then follow their behavior,? Meletis said. ?We find that these cells proliferate upon spinal cord injury, migrate toward the injury site and differentiate over several months.?

The study uncovers the molecular mechanism underlying the tantalizing results of the rodent and primate and goes one step further: By identifying for the first time where this subpopulation of cells is found, they pave a path toward manipulating them with drugs to boost their inborn ability to repair damaged nerve cells.

?The ependymal cells? ability to turn into several different cell types upon injury makes them very interesting from an intervention aspect: Imagine if we could regulate the behavior of this stem cell population to repair damaged nerve cells,? Meletis said.

Upon injury, ependymal cells proliferate and migrate to the injured area, producing a mass of scar-forming cells, plus fewer cells called oligodendrocytes. The oligodendrocytes restore the myelin, or coating, on nerve cells? long, slender, electrical impulse-carrying projections called axons. Myelin is like the layer of plastic insulation on an electrical wire; without it, nerve cells don?t function properly.

?The limited functional recovery typically associated with central nervous system injuries is in part due to the failure of severed axons to regrow and reconnect with their target cells in the peripheral nervous system that extends to our arms, hands, legs and feet,? Meletis said. ?The function of axons that remain intact after injury in humans is often compromised without insulating sheaths of myelin.?

If scientists could genetically manipulate ependymal cells to produce more myelin and less scar tissue after a spinal cord injury, they could potentially avoid or reverse many of the debilitating effects of this type of injury, the researchers said.

Provided by MIT

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Nanotechnology May Help Reconnect Nerves

U.S. researchers say they have created a nano-engineered gel that can enable severed spinal cord fibers to regenerate and grow.

Mice paralysed by spinal injuries have been able to walk again thanks to a treatment developed by scientists in the US. The therapy uses proteins that self-assemble into nano-fibers at the site of the injury, encouraging nerves to regrow.

Spinal cord injuries often lead to permanent paralysis and loss of sensation because the damaged nerve fibers can't regenerate, Northwestern University scientists said. Although nerve fibers or axons have the capacity to re-grow, they don't because they're blocked by scar tissue that develops around the injury.

The nanogel developed at the university's Feinberg School of Medicine inhibits formation of scar tissue and enables the severed spinal cord fibers to regenerate and grow, the scientists said.

The gel is injected as a liquid into the spinal cord and self-assembles into a scaffold that supports new nerve fibers. When the gel was injected into mice with a spinal cord injury, after six weeks the animals had a greatly enhanced ability to use their hind legs and walk.

"It's important to understand that something that works in mice will not necessarily work in human beings," said study leader Dr. John Kessler, who noted that if the gel is eventually approved for humans, a clinical trial could begin within several years.

The research is reported in the Journal of Neuroscience.

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Experimental Russian Stem Cell Treatments Credited for Woman's Progress

Experimental Russian stem cell treatments for spinal injury credited for woman's progress

Notice: The following excerpts are taken from the Grand Rapids Press. A link the the entire article is listed below, and is well worth the time to read.

When Kadi DeHaan took her first steps in December, two years after a car accident forced her into a wheelchair, she did it in typical Kadi style: low-key, nonchalant and with a confident grin.

Apparently, she knew all along she would walk away from her pink and black wheelchair and her customized leg braces, despite a spinal cord injury at chest level and a grim prognosis that she would never walk again.

It happened after two years of intensive therapy and six trips to Russia, where her stem cells were harvested and then injected into her spinal cord to restore nerves.

Kadi's progress is "very much a unique and wonderful thing," said physical therapist Sandy Burns, director of the Center for Spinal Cord Injury Recovery in Rockford, a clinic affiliated with the Detroit Medical Center.

No one can say for sure if nearly two years of experimental treatments or hours upon hours of physical therapy -- a trio of three-hour sessions every week -- led Kadi to where she is today.

Probably both, said Burns, whose clients sometimes head to Russia or Portugal or China for treatments that aren't approved in the U.S. and generally aren't covered by insurance.

The physical therapy is a very important component, "but it's definitely Russia," that put Kadi back on her own two feet, Kadi's mom, Bonnie, insisted. "There are just too many coincidences. Kadi knows that what she's got she got from Russia."

After fundraising dollars ran out more than a year ago, Kadi's parents took out a loan to pay for the trips to Russia. The three-year protocol recommended by Moscow doctors will cost in excess of $150,000.

At the time, Kadi had just a bit of feeling in her feet and could walk only with lots of help from custom-built leg braces and a walker.

Since then, she's given up the braces and is "tons stronger" and "a lot more independent," she said. She's a full-time student at Davenport University who quaffs Mountain Dew and confesses to sending text messages during class.

"I've seen a lot of changes. I've seen motor return, sensory return, everything," Kadi said.

She's so convinced of the gains made at the NeuroVita Clinic that she's planning her seventh trip there in August. Quite a change of attitude after she declared the first trip "the worst three weeks of my life."

Burns, who is quick to say her clinic does not endorse any of the alternative treatments, acknowledged that the stem cell injections do seem to make a difference, at least for Kadi.

"Folks that have gone there have, I think, consistently reported that they are noticing changes. They are feeling more," Burns said.

She tempers her optimism with the reality of what she sees every day: some of her clients will never accomplish half as much as Kadi has. Progress often depends upon the severity of the spinal injury, not just the region of the spine that was damaged.

That's why Burns doesn't make predictions about what her clients will eventually accomplish. But of course, she hopes Kadi continues to make great strides.

---

The Neurovita Clinic

Where: Moscow, Russia
What: Treats spinal cord injuries, degenerative disorders and some cancers with patient's own stem cells, which are harvested, grown and re-injected. Clinic moved away from use of embryonic stem cells because of compatibility issues.
Insurance: Because treatment is experimental and not performed here, U.S. insurance policies don't cover it.
Website: neurovita.ru/eng_index.html

The NeuroVita clinic was founded by neurologist Andrey S. Bryukhovetskiy in 2002. It's located on the campus of the Russian State Medical University and can accommodate 35 patients.

The clinic dabbled in embryonic stem cell treatments but now uses only autologous material -- that which is obtained from the patient -- because there are no problems with compatibility, not to mention politics and religion, according to the Web site.

About 11 of every 100 patients with spinal cord injuries walk again after the stem cell treatments, Bryukhovetskiy told them.

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Spinal Cord Injury Regeneration Hope

Scientists believe they are close to a significant breakthrough in the treatment of spinal injuries.

The University of Cambridge team is developing a treatment which could potentially allow damaged nerve fibers to regenerate within the spinal cord.

It may also encourage the remaining undamaged nerve fibers to work more effectively.

Spinal injuries are difficult to treat because the body cannot repair damage to the brain or spinal cord.

Although it is possible for nerves to regenerate, they are blocked by the scar tissue that forms at the site of the spinal injury.

Scientists believe they are close to a significant breakthrough in the treatment of spinal injuries.

The Cambridge team has identified a bacteria enzyme called chondroitinase which is capable of digesting molecules within scar tissue to allow some nerve fibers to regrow.

The enzyme also promotes nerve plasticity, which potentially means that remaining undamaged nerve fibers have an increased likelihood of making new connections that could bypass the area of damage.

Boosts rehabilitation

In preliminary tests, the researchers have shown that combining chondroitinase with rehabilitation produces better results than using either technique alone.

However, trials have yet to begin in patients.

Lead researcher Professor James Fawcett said: "It is rare to find that a spinal cord is completely severed, generally there are still some nerve fibers that are undamaged.

"Chondroitinase offers us hope in two ways; firstly it allows some nerve fibers to regenerate and secondly it enables other nerves to take on the role of those fibers that cannot be repaired.

"Along with rehabilitation we are very hopeful that at last we may be able to offer paralyzed patients a treatment to improve their condition."

'Ground-breaking'

Dr Yolande Harley, of the charity Action Medical Research which funded the work, said: "This is incredibly exciting, ground-breaking work, which will give new hope to people with recent spinal injuries."

Paul Smith, of the Spinal Injuries Association, said medical advances meant that spinal injuries had ceased to be the terminal conditions that they often once were, but they still had a huge impact on quality of life.

However, he warned against raising expectation before the treatment was fully tested on patients.

He said: "What often happens in a clinical setting is that you don't get to see the results you would have liked."

In the UK there are more than 40,000 people suffering from injuries to their spine, which can take the form of anything from loss of sensation to full paralysis.

The average age at the time of injury is just 19.

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Scientists Identify Gene that Helps Salamanders Regrow Limbs

University of Montreal researchers have identified a gene that allows limb regeneration in the axolotl, a salamander that lives in Mexican lakes.

The gene, called TGF-beta 1, controls the generation and movement of new cells, and allows the axolotl to regrow complex structures like limbs, tail, jaw, spinal cord and even parts of its brain.

Humans also have this gene. The difference is that in humans, instead of telling a limb to regenerate, the gene tells the wounded area to heal and form a scar. If scientists can find a way to manipulate TGF-beta in humans, it could lead to the ability to regrow organs and limbs, as well as treatments for spinal cord injury and severe burns.

In the study, the scientists used a drug that inhibited the gene in axolotls. The treated axolotls couldn't regrow their limbs, proving that TGF-beta plays a role in regeneration.

The salamander study is published in the November 28 issue of PLoS ONE.

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Simple Injection Shows Promise for Treating Paralysis

Paralyzed lab rodents with spinal cord injuries apparently regained some ability to walk six weeks after a simple injection of biodegradable soap-like molecules that helped nerves regenerate.

The research could have implications for humans with similar injuries.

"It will take a long time, but we want to offer at least some improvement, to improve quality of life for people with these injuries," materials scientist Samuel Stupp at Northwestern University in Evanston, Ill., told LiveScience. "Anything would be considered a breakthrough, because there's nothing right now."

The soap-like molecules contain a small piece of laminin, a natural protein important in brain development. After these molecules are injected into the body, they react with chemicals there, assembling themselves instantly into scaffolds of super-thin fibers just six billionths of a meter wide, roughly a hundredth a wavelength of orange light. They biodegrade after roughly eight weeks.

The scientists experimented with their molecules on dozens of mice and rats that experienced spinal cord injuries that paralyzed their hind legs, "the kind of very hard blow people might experience after falling off skiing slopes or getting in car accidents," Stupp said. His colleague, neurologist John Kessler, became active in this work after Kessler's daughter was paralyzed in a skiing accident.

After six weeks, damaged nerves regenerated enough for the paralyzed legs of the rodents to regain some ability to walk.

"There's a special scale to monitor how much function they regained, ranging from 0 to 21," Stupp explained. "At 21, function is perfect. At 6 or 7, limbs are just paralyzed, and the mice were just dragging them along. If you go to 9 to 12, the animal can now actually move the limbs. Not perfectly?awkwardly?but they move. So two or three points on that scale makes a huge difference."

"We've been able to go from a 7 to a 9 in the mouse, and in the rat, the highest was 12," he said. The findings are to be presented today at a meeting of the Project on Emerging Nanotechnologies in Washington, D.C.

The researchers are currently in talks with the FDA regarding their work and hope to start phase I clinical trials (for toxicity and safety testing) in humans two years from now, Stupp said. The idea he and his colleagues have for these molecules is to administer them within a day or so after spinal cord injuries, before scar tissue begins to form that can suppress healing. Past experiments have shown these molecules can actually turn neural stem cells (which might otherwise become scar cells) into neurons instead.

"Recovering every function a person had before an injury will probably be very hard," Stupp cautioned. "Even if people couldn't walk, if they could recover bladder function, that'd be a good thing. It's the first thing I'd want to recover."

The researchers now are developing versions of these soap-like molecules that could help with regeneration when it comes to other maladies such as Parkinson's disease, stroke, heart attacks, bone trauma or diabetes.

By Charles Q. Choi

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