Monday, September 26, 2005

Adult Stem Cell Research Treats Spinal Cord Injury Patient

I have known about this for some time, but because I didn't want to be guilty of the same hyping that is so often engaged in by some therapeutic cloning proponents, I waited until it was published in a peer reviewed journal.

Now it has been and the news is HUGE: Korean scientists have used umbilical cord blood stem cells to restore feeling and mobility to a spinal cord injury patient. I have no link, but I do have the report published in Cythotherapy, (2005) Vol 7. No. 4, 368-373.

The patient is a woman who has been paraplegic from an accident for more than 19 years. (Complete paraplegia of the 10th thoracic vertebra.) She had surgery and also an infusion of umbilical cord blood stem cells.

Note the stunning benefits: "The patient could move her hips and feel her hip skin on day 15 after transplantation. On day 25 after transplantation her feet responded to stimulation. On post operative day (POD) 7, motor activity was noticed and improved gradually in her lumbar paravertebral and hip muscles. She could maintain an upright position by herself on POD 13. From POD 15 she began to elevate both lower legs about 1 cm, and hip flexor muscle activity gradually improved until POD 41."

It goes on from there in very technical language.

The bottom line is this, from the Abstract: Not only did the patient regain feeling, but "41 days after [stem cell] transplantation" testing "also showed regeneration of the spinal cord at the injured cite" and below it. "Therefore, it is suggested that UCB multipotent stem cell transplantation could be a good treatment method for SPI patients."

We have to be cautious. One patient does not a treatment make.

Also, the authors note that the lamenectomy the patient received might have offered some benefit. But still, this is a wonderful story that offers tremendous hope for paralyzed patients.

Typically, it has been completely ignored in the American media (although it has gotten some foreign press attention). (Can you imagine the headlines if the cells used had been embryonic?)

One last point. This is a patient with a very old injury -- making the results even more dramatic.

By: Wesley Smith
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Thursday, September 22, 2005

Mice Walk Again in Stem Cell Study

WASHINGTON (AP) - Injections of human stem cells seem to directly repair some of the damage caused by spinal cord injury, according to research that helped partially paralyzed mice walk again.

The experiment, reported Monday, isn't the first to show that stem cells offer tantalizing hope for spinal cord injury; other scientists have helped mice recover, too.

But the new work went an extra step, suggesting the connections the stem cells form to help bridge the damaged spinal cord are key to recovery.

Surprisingly, they didn't just form new nerve cells. They also formed cells that create the biological insulation that nerve fibers need to communicate. A number of neurological diseases, such as multiple sclerosis, involve loss of that insulation, called myelin.

"The actual cells that we transplanted, the human cells, are the ones that are making myelin," said lead researcher Aileen Anderson of the University of California, Irvine. "We?re extremely excited about these cells."

The research is reported in Monday's issue of Proceedings of the National Academy of Sciences.

Stem cells are building blocks that turn into different types of tissues. Embryonic stem cells in particular have made headlines recently as scientists have attempted to harness them to regenerate damaged organs or other body parts. They're essentially a blank slate, able to turn into any tissue given the right biochemical instructions.

But they're not the only type of stem cell. Anderson and colleagues used fetal neural stem cells, which are slightly more developed than embryonic stem cells because they're destined to make cells for the central nervous system.

The researchers injured the spinal cords of mice and nine days later injected some with the human neural stem cells.

Four months later, the treated mice could again step normally with their hind paws. Mice given no treatment or an injection with an unrelated cell showed no improvement.

The question was what sparked that improvement. Injections of stem cells might simply stimulate the body to produce some healing factor, or they might directly repair damage themselves.

So Anderson injected the animals with diphtheria toxin, which kills only human cells, not mouse cells. The improvements in walking disappeared, suggesting the cells themselves were responsible for recovery.

"It was striking," Anderson said.

Finally, the researchers analyzed the actual mouse spinal cords to see what the human stem cells had turned into. The hope was that they would make neurons, or nerve cells, and some did.

But the bulk of the injected stem cells formed oligodendrocytes, a different type of cell that forms myelin, the insulation coating that is key for nerve fibers to transmit the electrical signals they use to communicate.

The toxin step was key to ensuring the transplanted cells themselves are functioning, and all researchers must provide such evidence because different types of stem cells almost certainly will work by different mechanisms in different tissues, said Doug Kerr, a Johns Hopkins University neurologist who is performing similar spinal cord research with embryonic stem cells.

Much more research must be done before testing stem cells in people with spinal cord injuries, Anderson said. One question is how soon after an injury cells must be administered to have any effect; no one knows how nine days in a mouse's life correlates to the post-injury period for a person. Also, the mice were bred to avoid immune system destruction of the human cells, and suppressing a person's immune system because of similar transplant rejection risk poses big problems.

"The last thing we want to do is take someone who's living a productive life - if confined, we all understand that - and make them worse," said Anderson, who said the work also shows the need to study all types of stem cells. "The exciting part is the potential is there."

The research was funded by the not-for-profit Christopher Reeve Foundation and the National Institutes of Health.

StemCells Inc. of Palo Alto, Calif., provided the fetal-derived stem cells.By: Wesley Smith
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Monday, September 05, 2005

Gradient Guides Nerve Growth Down Spinal Cord

University of Chicago - The same family of chemical signals that attracts developing sensory nerves up the spinal cord toward the brain serves to repel motor nerves, sending them in the opposite direction, down the cord and away from the brain, report researchers at the University of Chicago in the September 2005 issue of Nature Neuroscience (available online August 14). The finding may help physicians restore function to people with paralyzing spinal cord injuries.

Growing nerve cells send out axons, long narrow processes that search out and connect with other nerve cells. Axons are tipped with growth cones, bearing specific receptors, which detect chemical signals and then grow toward or away from the source.

In 2003, University of Chicago researchers reported that a gradient of biochemical signals known as the Wnt proteins acted as a guide for sensory nerves. These nerves have a receptor on the tips of their growth cones, known as Frizzled3, which responds to Wnts.

In this paper, the researchers show that the nerves growing in the opposite direction are driven down the cord, away from the brain, under the guidance of a receptor, known as Ryk, with very different tastes. Ryk sees Wnts as repulsive signals.

"This is remarkable example of the efficiency of nature," said Yimin Zou, PhD, assistant professor of neurobiology, pharmacology, and physiology at the University of Chicago. "The nervous system is using a similar set of chemical signals to regulate axon traffic in both directions along the length of the spinal cord."

It may also prove a boon to clinicians, offering clues about how to grow new connections among neurons to repair or replace damaged nerves. Unlike many other body components, damaged axons in the adult spinal cord cannot adequately repair themselves. An estimated 250,000 people in the United States suffer from permanent spinal cord injuries, with about 11,000 new cases each year.

This study focused on corticospinal neurons, which control voluntary movements and fine-motor skills. These are some of the longest cells in the body. The corticospinal neurons connect to groups of neurons along the length of spinal cord, some of which reach out of the spinal cord. They pass out of the cord between each pair of vertebrae and extend to different parts of the body, for example the hand or foot.

Zou and colleagues studied the guidance system used to assemble this complex network in newborn mice, where corticospinal axon growth is still underway. Before birth, axons grow out from the cell body of a nerve cell in the motor cortex. The axons follow a path back through the brain to the spinal cord.

By the time of birth, the axons are just growing into the cord. During the first week after birth they grow down the cervical and thoracic spinal cord until they reach their proper position, usually after seven to ten days.

From previous studies, Zou and colleagues knew that a gradient of various Wnt proteins, including Wnt4, formed along the spinal cord around the time of birth. Here they show that two other proteins, Wnt1 and Wnt5a are produced at high concentrations at the top of the cord and at consecutively lower levels farther down.

They also found that motor nerves are guided by Wnts through a different receptor, called Ryk, that mediates repulsion by Wnts. Antibodies that blocked the Wnt-Ryk interaction blocked the downward growth of corticospinal axons when injected into the space between the dura and spinal cord in newborn mice.

This knowledge, coupled with emerging stem cell technologies, may provide the most promising current approach to nervous system regeneration. If Wnt proteins could be used to guide transplanted nerve cells--or someday, embryonic stem cells--to restore the connections between the body and the brain, "it could revolutionize treatment of patients with paralyzing injuries to these nerves," Zou suggests.

"Although half the battle is acquiring the right cells to repair the nervous system," he said, "the other half is guiding them to their targets where they can make the right connections."

"Understanding how the brain and the spinal cord are connected during embryonic development could give us clues about how to repair damaged connections in adults with traumatic injury or degenerative disorders," Zou added.
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