The Failure, and Unexpected Promise, of Stem Cell Treatment for TBIs

Stem cells were supposed to help regenerate or replace damaged neurons. They didn't. But they may stop the body from doing more damage to itself

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By Nabeeha Chaudhary
Population Health Scholar
University of Texas System
Phd Student in Media Studies
UT Austin Moody College of Communication

 
 

Millions of Americans suffer from traumatic brain injuries (TBI) each year, but few therapies exist that can repair even minimal damage from severe TBI. As a result, treatments tend to be supportive rather than reparative. Dr. Charles Cox and his team are working to change that.

“Traumatic brain injury is really two things: a primary injury and a secondary injury,” says Cox, Professor of Pediatric Surgery at McGovern Medical School at UTHealth in Houston. “The initial impact––on the ground or with an object––is the primary kinetic injury, and nothing can be done about that kinetic disruption of tissue. But then there is a secondary sequence of reactions as the body’s innate immune system responds to the damaged tissue, generating brain inflammation that ends up killing neurons.”

Cox’s research is centered around using stem cell therapy to limit this collateral inflammatory damage that follows the immediate trauma of brain injury, so that some of the damaged tissue has a chance to recover.

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“Inflammation in general is a funny thing,” says Cox, who is co-director of the Memorial Hermann Red Duke Trauma Institute. “It’s part of our innate immune system and is required for any kind of wound healing. And it was really good when we humans lived in a cave.”

The problem, says Cox, is that it can be far too blunt an instrument now that we have the tools of modern medicine to stabilize patients and protect healthy tissue. He gives the example of a man bitten by a saber-toothed tiger 100,000 years ago. The massive inflammatory response from his body would either help solve the problem—by killing the damaged tissue so that the healthy tissue could survive—or he would die. No one was going to suture up the wound, glue it together, or prescribe antibiotics

This kind of binary response sacrifices a lot of surrounding tissue for the best chance at total organism survival. It made sense out on the savannah. In a modern ICU, however, it’s not adaptive. Doctors have other means for protecting the healthy tissue, and inflammation becomes a hindrance to healing.

The realization that stem cells could fight this inflammation, says Cox, is partially the product of the failure of previous stem cell therapy approaches.

“When we started,” says Cox, “the idea was that these cells could serve as replacement building blocks to damaged tissue. But it didn’t work.”

Rather than stimulate the generation of new neurons in the brain, the cells instead got sequestered in other organs like the lungs and the spleen.

Once there, however, the stem cells did something interesting. They interacted with the immune cells in these organs, prompting them to release anti-inflammatory agents. Signals from the spleen and lungs then polarized the immune cells in the brain to change to a more reparative phase. By limiting inflammatory response, brain tissue is preserved, leading to better neurocognitive outcomes.

Clinical trials, first in pediatrics and then in adults (both ongoing), have shown how this treatment can reduce brain inflammation. Cox and his team extract bone marrow from patients and separate specific cells which are then re-administered within 24 to 36 hours after the injury. These cells then trigger the anti-inflammatory cascade.

Their phase II trial in pediatric TBI treatment is about 80% complete and the adult phase II trial is about 30% done, with promising results in both trials.

The potential efficacy of this treatment is testament to the importance, says Cox, of believing the data instead of your preconceived notions about it.

“Our whole initial paradigm was completely wrong,” he says. “We were completely off base. But some of those things have led to our most productive discoveries.”