Stem cells taken from umbilical cord blood, then given intravenously along with a drug known to temporarily breach the brain’s protective barrier, can dramatically reduce stroke size and damage, Medical College of Georgia and University of South Florida researchers say.
“What we found was interesting, phenomenal really,” says Dr. Cesario V. Borlongan, neuroscientist and lead author of the study published in the October issue of the American Heart Association journal, Stroke.
Researchers first gave the drug, mannitol, to provide temporary passage through the blood-brain barrier then transfused human umbilical cord blood cells into a stroke animal model. When used in the first hours and days following a stroke, stroke size decreased by 40 percent and resulting disability was significantly reduced.
“We have two potential routes of delivery, intravenously through the jugular vein or directly transplanting the cells into the brain,” says Dr. Borlongan. Initial studies comparing the two approaches showed the intravenous approach ineffective until researchers added mannitol.
“Intravenous delivery of (human umbilical cord blood cells) poses an efficient and non-invasive cell therapy for (central nervous system) disorders characterized by a narrow therapeutic window,” the researchers write. “A multi-drug treatment for stroke may be realized via a cell-based therapy that involves routine clinical IV infusion of stem/progenitor cells allowing the biological release of a cocktail of trophic factors into the brain.”
Although no evidence could be found of the low-dose umbilical cord blood stem cells themselves in the brain three days after the treatment, evidence of neuroprotection was clear, Dr. Borlongan says. “The critical factors we have seen elevated in this stroke animal model are the neurotrophic factors.”
“This is an important finding because it shows that umbilical cord blood cells do not have to become new brain cells to protect the brain,” says Dr. Paul R. Sanberg, neuroscientist at the University of South Florida and a co-author on the study. Human umbilical cord blood stem cells used for the study were obtained from Saneron CCEL Therapeutics, Inc., in Tampa, Fla., a USF spin-off company researching clinical applications for cord blood cells.
An article in the same issue of Stroke by the USF researchers led by Dr. Alison Willing, neuroscientist, shows that 10 times the number of stem cells or more would be needed to produce similar results if cells were given intravenously without any help crossing the blood-brain barrier.
The MCG-led study used 200,000 umbilical cord blood cells and a low dose of mannitol, a sugar alcohol and diuretic whose uses include helping chemotherapeutic agents reach the brain. The USF study showed a dose-response relationship with significant recovery in behavioral performance when 1 million or more cells were given, Drs. Willing and Sanberg and their colleagues report.