Originally created 04/08/06

Cells might aid stroke recovery



Human stem cells from bone marrow helped improve the recovery of rats that had suffered strokes and newborn rats that had injuries similar to cerebral palsy, researchers at Medical College of Georgia reported Friday.

These adult stem cells, called multipotent adult progenitor cells, have a number of advantages over the more controversial embryonic stem cells and could begin trials in humans next year, according to the company that produces them.

In work that was presented Friday at the annual meeting of the American Academy of Neurology, the MCG team showed that rats that were induced to have a stroke and then given the marrow-derived cells seven days later had up to a 25 percent increase in function. For instance, an untreated rat with a stroke cannot cross a balance beam, but the treated animals can, said Cesario Borlongan, the director of stem cell research in the Department of Neurology at MCG.

"It will not traverse the whole length, but at least it can move a short distance," Dr. Borlongan said.

And that is why the researchers are cautious about predicting what the cells can do in people, said David Hess, the chairman of the MCG Department of Neurology.

"What we don't know is what the 25 percent recovery in a rat equates to in a human," Dr. Hess said. "Is that wheelchair to a cane? A cane to a walker? We don't know what that is."

The recovery came despite the fact that few of the transplanted cells survived in the brains of the rats. Instead, there was a proliferation of the brain's own cells in the injured area, Dr. Borlongan said.

"What we think is going on is these transplanted cells are secreting some trophic factors or growth factors and they are helping the injured but remaining viable cells to survive better," he said. "And at the same time probably stimulating the formation of new cells within the injured brain."

That ability to deliver more than one factor and to sense what is needed is an important advantage, said Gil Van Bokkelen, the chairman and chief executive of Athersys Inc., which manufactures the cells, called MultiStem.

"It makes intuitive sense to us that if you have the ability to deliver a cell, for example, that is capable of producing multiple factors in parallel and furthermore that's wired to sort of sense what the local microenvironment (in the brain) is so it can respond accordingly, that you're probably going to get a much more powerful effect from that kind of approach," Dr. Van Bokkelen said.

Also important is that these human cells work in rats and there appears to be no need to try to match characteristics between the donor and patient, as in other transplants.

"It seems that these MAPC cells are not rejected," Dr. Hess said. "They are tolerant" of the body's own cells.

The cells were discovered in 2002 by Catherine Verfaillie, the director of the Stem Cell Institute at the University of Minnesota, who also found that putting them into rat brains brought about similar results. But those rats had been given an immune-suppressing drug typically given to transplant patients, she said.

"The fact that they could see this result without having to immunosuppress the animal is indeed something that suggests that it might be possible to do this even without any matching," Dr. Verfaillie said.

The MCG team also is now testing a different delivery system. The rats in the study had the cells delivered directly into their brains, but Dr. Borlongan is investigating whether using an IV would work. That would be important if it were to become a therapy for people, because any hospital in the country could deliver it through IV, Dr. Hess said.

Athersys, which can mass produce the cells, is hoping to begin human trials treating acute heart attacks next year and would like to begin clinical trials in stroke victims next year, too, Dr. Van Bokkelen said. Mass producing the cells would be particularly important if it proved effective.

"The fact that you could actually manufacture it on that kind of basis and then deliver it without having to go through this extensive matching process, and the fact that you can cryopreserve (freeze) the cells, sort of simplifies the whole process potentially," Dr. Van Bokkelen said.

Reach Tom Corwin at (706) 823-3213 or tom.corwin@augustachronicle.com.

WHAT'S NEXT

Athersys Inc. of Cleveland is hoping to begin human trials next year with the MultiStem multipotent adult progenitor cells featured in the Medical College of Georgia study.