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A Stem Cell Christmas Miracle?

| Source: rppi.or

A report earlier this week that South Korean researchers have used stem cells derived from umbilical cord blood to help a woman with a damaged spinal cord walk again is bound to re-ignite the battle over human embryonic stem cell research.

The researchers say they harvested embryonic stem cells from blood taken from umbilical cords and injected them into the spine of a 37-year-old woman named Hwang Mi-soon. Ms. Hwang, who has been chair-bound for nearly two decades, took several steps using a walker at a press conference and declared her progress a “miracle.” And a miracle it is: Cord blood stem cells were injected directly into her injured spinal cord on October 12; a month a half later, she is able to perambulate somewhat.

“I would be very skeptical of drawing any conclusions from one case with no controls,” says Evan Snyder, director of the Stem Cell and Regeneration program at the Burnham Institute in La Jolla, California. “The extent of my skepticism is incredibly high based on what is known about the biology of umbilical cord cells.” Snyder’s skepticism seems amply justified by current scientific results.

Heretofore only lab animals with injured spinal cords have been able to walk again after nerve cells derived from human embryonic stem cells have been installed in them. A Florida biotech startup, Saneron CCEL Therapeutics, which has evidently been working with the South Korean researchers, reported earlier this year that infusing human umbilical cord blood stem cells into the injured spines of rats “led to some recovery of function” although “none of the rats walked following treatment.”

The researchers don’t know exactly what the stem cells are doing to promote healing. Earlier studies found that infused umbilical cord blood stem cells could somehow repair stroke damage in the brains of lab rats, though only a few of the cells actually seem to differentiate into cells resembling neurons. One of the South Florida researchers earlier estimated that only one in a million of the umbilical cord blood stem cells could differentiate into nerve-like cells.

Another experiment in which a young girl was transfused with umbilical cord stem cells in the hope of repairing her brain found, upon autopsy, no nerve cells derived from the cord blood cells.

One other factor needs to be considered: Unlike the Korean case where cells were injected into an old injury, all of the other experiments involved trying to repair damage shortly after it occurred. This is because scarring generally blocks access to the damaged area. It’s not at all evident how umbilical cord stem cells could get around this problem.

Which is not to say that umbilical cord blood stem cells are not useful. Transplanted human umbilical cord blood stem cells were first used in Paris in 1988 to treat a 5-year-old boy with Fanconi anemia. More recently, umbilical cord blood stem cells have been used to cure leukemia in adults.

Once the malfunctioning blood-forming bone marrow of a leukemia patient is destroyed by radiation, the patient is infused with umbilical cord blood stem cells. The transplanted cells nest in the patient’s bones, where they produce all the healthy components of blood: red cells, white cells, and platelets. Transplanted umbilical cord blood stem cells seem less Prone to cause immune system problems than adult bone marrow cells, possibly because of their immaturity.

The South Korean researchers are calling their stem cells “multipotent” because they are not regenerating blood-forming tissues, but are somehow exhibiting the extra power of repairing nerves. But given the failure to find regenerated nerve cells in earlier experiments, what is going on? Snyder notes that it’s possible that the actual injection itself caused changes in Ms. Hwang’s spinal cord. Or she may be responding to more intense levels of Physical Therapy that she received after the transplant. “For all we know, holy water could have been just as effective as the umbilical cord cells,” Snyder says.

Engaging in a bit of pure speculation on my part, perhaps what has occurred is related to a recent finding by researchers at Kansas State University. The Kansas researchers isolated what they believe to be stem cells from the matrix of umbilical cords of pigs and humans, not from umbilical cord blood. The matrix, called Wharton’s jelly, cushions blood vessels in the umbilical cord. The researchers have been able to propagate those cells for more than 80 generations, and have been able to direct them to differentiate into cells that look a lot like neurons. “Our results indicate that Wharton’s jelly cells can be expanded in vitro, maintained in culture, and induced to differentiate into neural cells. We think these cells can serve many therapeutic and biotechnological roles in the future,” said Kathy Mitchell, the lead researcher on the project. Perhaps the umbilical cord blood stem cells used by the Korean researchers also contained the apparently more versatile stem cells derived from Wharton’s jelly?

Meanwhile, human embryonic stem cell researchers have not been idle. The California-based biotech company Geron paid for the research that first isolated and then cultured human embryonic stem cells in 1998. According to Geron CEO Thomas Okarma, the company is aiming to file an investigational new drug application with the U.S. Food and Drug Administration (FDA) requesting permission to begin clinical trials using Glial Cells derived from embryonic stem cells to repair damaged spinal cords in 2005 or early 2006. (Glial cells are the cells that surround and support nerve cells.) Geron’s research shows that transplanted glial cells derived from human embryonic stem cells repair the crushed spinal cords of rats by encouraging the restoration of protective Myelin sheathing to damaged nerves. Myelin acts like insulation that keeps nerves from short-circuiting. After treatment, paralyzed rats regained sensation and most of their ability to walk using their hind legs.

Geron plans to transplant the glial cells into patients who have recently had their spinal cords crushed. The first trial would focus on patients whose lower extremities are paralyzed and who have lost bladder control. If all goes well with those trials, the second part of the trial would treat patients with spinal injuries in their necks that require them to use respirators. If such patients can regain their ability to breathe, that would be convincing proof of the treatment’s success. Okarma notes that Geron’s application to the FDA will be “five years before our critics ever said embryonic stem cells would hit human trials.”

These different avenues of potential therapeutic benefit raise a politico-scientific question: human umbilical cord stem cells or human embryonic stem cells? Unlike human embryonic stem cells, umbilical cord stem cells do not raise moral hackles and are not tangled with the controversy over abortion. So why not just drop research on embryonic stem cells and proceed with the uncontroversial umbilical cord cells?

Because the two approaches don’t offer the same advantages. For example, one current problem with stem cells from umbilical cord blood is that they do not continually renew in culture without differentiating like human embryonic stem cells do. So instead of deriving stem cells for each individual patient from different umbilical cords, Geron proposes to create master cell banks of already derived embryonic stem cells that can be used to treat thousands of patients. Such stem cells and the cells derived from them can be standardized and production can be scaled up to produce therapeutic quantities for thousands of patients. However, it is possible that the just-discovered umbilical cord stem cells derived from Wharton’s jelly might similarly be standardized.

For the sake of Ms. Hwang and millions (including about 250,000 Americans) who live with spinal cord injuries, let us hope that the South Korean research can be reliably replicated and improved upon. However, only more research will tell whether the promise of adult umbilical cord and embryonic stem cells will be fulfilled. Various lines of research should be pursued simultaneously to insure the best chance of discovering effective future treatments. It may well turn out that adult stem cells are good treatments for certain diseases, umbilical cord stem cells work best for others, and embryonic stem cells are better at curing still different maladies. Contrary to the claims of bioconservatives, it is not either adult and umbilical cord stem cells or embryonic ones; for the sake of millions of suffering patients, it’s necessary to forge ahead on all three fronts.

Ronald Bailey is Reason’s science correspondent. His new book, Liberation Biology: A Moral and Scientific Defense of the Biotech Revolution will be published in early 2005.

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