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Some Stem Cells Heal Differently, Researchers Said

Date (2015-04-27)

Forget the traditional view that certain stem cells will heal by becoming replacement cells for damaged tissue. The real power of these cells comes from their ability to regulate the immune response and spark the body’s own regenerative machinery, leading researchers said.

The key will be what kind of cells are given and when they are used.

Georgia Regents Univer­si­ty last week held a Regen­erative Medicine and Cell­ular Therapy Research Symposium that attracted speakers from across the country.

While mesenchymal stem cell therapy has always attracted attention for the potential of these cells to differentiate into other cells of the body – such as bone or muscle – once they are given to patients, that’s not going to be what heals them, said Dr. Arnold I. Caplan of Case Western Reserve University, who is referred to as the “Father of the Mesenchymal Stem Cell” for his early work.

It is rather these cells’ ability to home in on the site of injury, sense the microenvironment of that injury and deliver a “drug store” of chemicals that can both modulate the immune response and trigger an innate regenerative response, Caplan said.

These cells, which are derived from blood vessel cells, are in great quantities in children but diminish over time. Thus the body begins to lose that ability to regenerate in an injury, such as a heart attack, he said. Adding these cells, called MSCs for short, could aid the healing process, Caplan said.

The cells stop the ongoing damage of the injury and “they stop the immune system from overreacting, doing other damage,” he said. “They get the stem cells that are in the heart to actually plug the holes of the cells that drop dead. That’s the regenerative part.”

The enormous potential of these cells can be seen in the nearly 500 clinical trials looking at using them against a wide-ranging number of diseases, from diabetes to multiple sclerosis to Crohn’s disease to fighting injuries such as heart attack or stroke. Success rates have varied, in part because of potency and timing, Caplan said.

For instance, Dr. David Hess, chairman of the GRU Department of Neurology, served as the lead clinical investigator looking at a type of that cell called MultiStem from Athersys Inc. to treat stroke. While Hess said the original intent was to limit the trial to giving the therapy within 24-36 hours, it was widened to 48 hours because of technical issues that made it difficult to find patients in that shorter timeframe. Results for those patients who received it within 36 hours were much better, Hess said.

“There’s a time limit of maybe 12 to 36 hours where these cells are probably going to have the greatest impact,” he said, and part of that may be due to the freshness of the injury. Caplan said the results should be encouraging.

“If they can do it within 36 hours, in general that is like 95 percent of the (stroke) patients,” he said. “They could get 95 percent of the patients. If it has the same clinical effect that they reported, that’s awesome.”

Working in stroke is also an advantage because, outside of a clot-busting drug that must be given within hours of a stroke, “there’s nothing really out there,” Hess said. “You don’t have to compete against really anything.”

The stem cell therapy has also shown promise against MS “but it is a crowded field, there’s a lot of therapeutics,” he said. “To enter that field you have to compete against established therapeutics and good companies.”

There is also the issue of potency, of how many cells are given, and the response, which can vary widely from person to person, and from sample to sample, Caplan said. But one thing they have shown is a lack of adverse events from the trials in people that have been conducted so far, which should cause the Food and Drug Administration to allow greater early use in people instead of its current model of handling them the way it does new drugs, Caplan said.

“We know these cells are going to do no harm,” he said. Even if it doesn’t work in half the patients who use it, which has been the outcome in some cases, the cells “should still be used in that context,” Caplan said.

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