The effects of multipotent adult progenitor stem cells on stroke recovery were the focus of two recently published papers that include researchers at the Institute for Stroke and Cerebrovascular Disease at UTHealth.
Results of a pre-clinical study led by UTHealth researchers that examined the effects of MultiStem®, a human bone marrow stem cell product, were published in a recent issue of the journal Stem Cells. Results of a phase 2 clinical trial of MultiStem®, which included McGovern Medical School researchers, were published in the journal Lancet Neurology.
“In our preclinical studies, we’ve found that these stem cells preferentially migrate to the spleen and as a result, we’re learning about how the spleen then sends messages to the brain. After a stroke, the spleen sends signals that contribute to inflammation, which can create an environment in the brain that is detrimental to healing,” said Sean I. Savitz, senior author of the preclinical trial and professor and the Frank M. Yatsu Chair in Neurology at McGovern Medical School. “Injecting MultiStem® changes the signals coming from the spleen, tamping down the inflammatory response, and allowing the brain to recover.”
When the spleen was removed in preclinical studies, the stem cells didn’t work as well, said Savitz, who also serves as the medical director of stroke at Memorial Hermann Mischer Neuroscience Institute.
UTHealth was the first in the country to treat an acute stroke patient with stem cells. The patient received the treatment at Memorial Hermann-Texas Medical Center.
Early data from the UTHealth preclinical studies of MultiStem contributed to the design of the phase 2 randomized, double-blind, placebo-controlled clinical trial. Savitz was on the study’s design team and the principal investigator for UTHealth. Authors of the study were led by David C. Hess, M.D., professor of neurology at Medical College of Georgia, and Robert W. Mays, Ph.D., vice president of Regenerative Medicine at Athersys, Inc., a biotechnology company that is developing MultiStem.
Researchers found that there were no differences in 90-day outcomes for patients treated at 48 hours post-stroke but there were statistical differences in patients treated within 36 hours.
“For patients given MultiStem at 36 hours, there was evidence of a treatment effect that indicated patients may have benefited from the cells. There was an improvement in outcome and reduction in complications,” Savitz said. “They had fewer days in the hospital and fewer cases of secondary infection – 16 percent in the group treated with stem cells versus 47.5 percent in the untreated group. As the most advanced study conducted on stem cells for acute stroke, the trial showed promising and consistent results across several outcomes.”
Savitz said he theorizes that at 48 hours, the spleen may have unleased too many damaging signals for the stem cells to have an effect. “Our clinical studies have shown that the spleen is already responding to stroke within 24 hours of stroke onset,” he said.
With that knowledge, Athersys and researchers including Savitz are planning now for the third phase of clinical testing using a treatment window of 18 to 36 hours.