Human umbilical cord blood cells may widen treatment window for stroke

An experimental treatment that spares disability from acute stroke may be delivered much later than the current three-hour treatment standard – a potential advance needed to benefit more stroke victims.

Researchers at the University of South Florida found that human umbilical cord blood cells administered to rats two days following a stroke greatly curbed the brain's inflammatory response, reducing the size of the stroke and resulting in greatly improved recovery. The rats' inflammatory response to injury from stroke peaked 48 hours after the brain attack, which was when intravenous delivery of the cells appeared most beneficial.

"We were very surprised," said principal investigator Alison Willing, PhD, a neuroscientist at the USF Center of Excellence for Aging and Brain Repair. "In some animals, the stroke initially damaged half the brain, but after treatment with the cord blood cells they were functioning normally.

"These findings show we are able to rescue neurons at a time when most research suggests they are already dead."

The only drug currently approved for ischemic stroke treatment is tPA (tissue plasminogen activator), which breaks up blood clots – the cause of most strokes. However, tPA must be given within three hours following a stroke to be effective and few patients arrive at the hospital quickly enough to receive it. Even when a patient meets the recommended three-hour treatment criteria, smaller hospitals often lack ready access to a CT scan, a test needed to rule out a hemorrhagic stroke caused by a burst blood vessel. The drug can worsen this less common type of stroke.

"New and more flexible treatments are needed to help more patients," Dr. Willing said. "Cord blood treatment in rats is successful in alleviating, even eliminating, the disabling effects of both ischemic and hemorrhagic stroke. What's more, the treatment can be delivered much later than the current strict three-hour therapeutic window."

The USF study challenges the notion that nerve cells inevitably die quickly in the core region of the brain most severely deprived of oxygen and nutrients when a stroke hits. Instead, the researchers suggest, many nerve cells within ground zero of the attack, like those in mild to moderately damaged outlying areas, may succumb over several days through a slower, more orderly process known as apoptosis, or programmed cell death.

"This delayed death would permit more time to deliver neuron-sparing treatments than originally thought," Dr. Willing said.

The USF researchers continue to investigate the ways cord blood cells aid stroke recovery in animals, and will begin a study to determine the timing of brain inflammatory responses in acute stroke patients.

Researchers working with Dr. Willing were Jennifer Newcomb, Ted Ajmo, Lisa Collier, Cyndy Davis Sanberg, PhD; Keith Pennypacker, PhD; and Paul R. Sanberg, PhD, DSc. The USF study was conducted with Saneron CCEL Therapeutics, a USF-spinout biotechnology company developing cell therapies for deadly and debilitating disorders. Dr. Sanberg is a cofounder of Saneron CCEL, and Dr. Willing is a consultant.