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A missing piece of stem cell brain repair puzzle discovered

USF Health distinguished neuroscientist Cesar Borlongan, PhD, has spent much of his career focused on advancing stem cell therapy for brain disorders, including stroke and traumatic brain injury.

His work has included investigating how to harness stem cells produced by the body itself to repair or prevent brain damage. Because they originate in the person being treated, these “endogenous” stem cells are recognized as “self” by the immune system and unlikely to trigger a potentially harmful response.  If even small numbers could be coaxed to proliferate and honed to the damaged area of the brain, the benefit could be substantial.

Scientists doubt that endogenous stem cells alone can repair a sick or injured brain. A newly published study led by Dr. Borlongan bolsters evidence that indeed they cannot.

But the more compelling finding reported by his USF team was this:  Transplanted stem cells were critical to guide newborn stem cells arising in a particular part of the brain (known in scientific parlance as a neurogenic niche) to the injured site, promoting functional recovery in an animal model of traumatic brain injury.

In essence, Borlongan and colleagues present a new view of how transplanted stem cells mediate brain repair.

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Cesar Borlongan, PhD

“I think our most intriguing observation was that stem cells are quite smart,” said Borlongan, who directs the USF Center for Aging and Brain Repair.

“The healthy and viable (transplanted) stem cells pave the way and form the biobridge that aids the journey of endogenous stem cells towards the injured brain tissue,” he said. “Most likely the (transplanted) cells were attracted to both a cell survival cue released by the neurogenic brain niche and the cell death signal released by the injured brain. In between these two survival and death depots, the stem cells build the biobridge.”

Once this “biobridge” is built, the hardworking transplanted cells appear to relinquish the task of carrying on repair to the brain’s host stem cells.

Previous studies have shown that even when millions of stem cells are transplanted into a sick or injured brain, only a few survive.

“Our biobridge observation provides a missing piece of the story about stem cell repair,” Borlongan said. “The transplanted stem cells actively work at night, clandestinely recruiting the new host cells, and by daytime when the biobridge is established, they disappear.”

The bone-marrow derived stem cells used in the USF study (SanBio Inc. SB632 cells) do not divide as prolifically as other types of stem cells or persist over time, so the risk of brain tumors or cancer following transplantation is highly unlikely, Borlongan notes.

A limited clinical trial to test the transplant of SB632 cells in patients with traumatic brain injury was recently approved by the Food and Drug Administration, based in part on the USF study

While the preclinical research is promising, Dr. Borlongan and others in the field of regenerative neuromedicine have plenty of challenging work ahead — from understanding the signaling cues needed to properly remodel the injured brain and finding drugs that may promote biobridge formation to identifying patient populations most likely to benefit from stem cell therapy.