Stem Cell Transplants Improve Recovery in Animal Models for Stroke, Cerebral Palsy

A single dose of adult donor stem cells given to animals with neurological damage can significantly enhance recovery, researchers say.

Using a commonly utilized animal model for stroke, researchers administered 200,000 to 400,000 human stem cells into the brains of animals with significant loss of mobility and other functions. The stem cells used in the study were a recently discovered stem cell type called multipotent adult progenitor cells, or MAPCs.

Motor and neurological performance in the animals improved 25 percent, said Dr. Cesario V. Borlongan, a neuroscientist at MCG and Augusta’s Veterans Affairs Medical Center.

“These are not going to be cures, but this level of recovery is significant. If somebody can go from a wheelchair to a cane, that is a big improvement,” Dr. Hess said.

Adult animals were tested across a range of standardized tasks both before and after a surgically induced stroke.

Following the stroke, both control animals and those that received a single injection of stem cells were evaluated for up to two months. Animals treated with stem cells had improved strength, balance, agility, fine motor skills and tissue recovery.

“A single dose of the cells produce robust behavioral recovery at an early period posttransplantation, and the recovery was durable, lasting up to two months, which was the entire length of this study,” Dr. Borlongan said. “Furthermore, animals continued to show improvement over time.” In the newborn model of ischemic injury, enhanced recovery took place within two weeks.

Even though fewer than 1 percent of the transplanted cells were present two months later, animals receiving treatment developed new neurons, apparently formed from endogenous stem cells. “The mechanism that we are putting forward is these donor cells are secreting nourishing trophic factors that are helping the host brain cells survive and stimulating stem cells from the host to multiply,” Dr. Borlongan said.

To help mimic potential clinical scenarios for stroke victims, transplants were performed seven days after the initial injury. The drug, tPA, must be administered within three hours of a stroke, a window most patients miss.

In the adult stroke model, MCG researchers found stem cell treatment increased the number of injured cells that survived just outside the area of greatest damage, also referred to as the ischemic core, by up to 20 percent.

“Up to this point, all the treatment approaches, including transplantation and tPA, cannot get rid of that ischemic core,” Dr. Borlongan said. “But outside of that core is a lining, the penumbra, which if you do not treat over time becomes part of the core. We are showing that even one week after a stroke, we are able to increase the number of cells surviving along that penumbra, and that is how we feel it is producing significant recovery.”

Animals in a model of cerebral palsy, a condition caused by an ischemic injury before or during birth, also improved at least 25 percent more than controls. Rodent stem cells were used in this model. A larger percentage of donated cells survived and within two weeks matured into neurons in the young, more pliable brains, Dr. Borlongan said. Also, close donor matching seemed unnecessary. Unmatched transplants from the same species and genetically identical transplants yielded comparable results.

Athersys, Inc., a Clevelandbased biopharmaceutical company, funded the research in which previously frozen human or rodent multipotent adult progenitor cells (MultiStem™) were thawed and injected directly into the brain.

Researchers believe MultiStem™ cells help in multiple ways, for example by producing factors that limit tissue damage and stimulate repair, according to Dr. Gil Van Bokkelen, the company’s chair and chief executive officer. The cells also can safely mature into a broad range of cell types and can be produced on a large scale.

In extensive animal testing, the mature stem cells have been shown to be safe and generally do not require close genetic matching, according to company executives. Another advantage is immunosuppressive drugs do not appear to be required, as they are with other types of stem cell treatment.

Although they have not specifically looked at whether stem cell therapy might be useful months after an ischemic event, the researchers believe early therapy likely will be the most successful.

They already are working with the Food and Drug Administration to begin clinical trials within the next few years.

In preparation for potential clinical use, the researchers are pursuing transplants in larger animal models and studying how MultiStem™ cells work in living human brain tissue housed at the MCG Human Brain Bank.