Regenerating Hope: How researchers are working to restore brain function
Masato Nakafuku, MD, PhD, is a researcher in Developmental Biology and professor, Department of Pediatrics, University of Cincinnati College of Medicine and an Ohio Board of Regents Eminent Scholar.
Kickstarting the brain: Dr. Masato Nakafuku studies what makes stem cells in the brain get busy after injury.
A Cincinnati Children’s Research Team Shows that Brain Cells – and Function – Can Be Restored
A Cincinnati Children’s Research Team Shows that Brain Cells – and Function – Can Be Restored
Cut your finger and your skin cells go into overdrive. Break a bone and repair starts immediately. But get an injury to the brain and spinal cord, and the body’s normal healing mechanism just sits there.
Masato Nakafuku, MD, PhD, wants to know why.
It’s not that the brain lacks the ability to heal, although until recently that’s what scientists thought – the brain was perceived as a “nonregenerative” organ. But in 1992, Canadian researcher Samuel Weiss turned that theory on its ear when he confirmed the presence of stem cells in the brain.
Merely having the capacity to repair itself isn’t enough, however. “We know that after damage, nothing miraculous happens to start the healing,” Nakafuku says. “Even if the stem cells are there, they’re not doing much.”
So he and his research team in the Division of Developmental Biology at Cincinnati Children’s are working on figuring out why not, and how they can change it.
Releasing Inhibitions
Working with animal models, Nakafuku and his team started with a fairly simple premise.
“Maybe the stem cells are trying to do something but can’t,” Nakafuku says. “If we can find a key mechanism that is inhibiting their activity and release them from that inhibition, something could happen.”
They set out to see if they could “uninhibit” the stem cells that naturally reside in the brain to regenerate after injury. To do this, they induced ischemia in rats, depriving the brain of blood supply and causing death to the brain tissue, in much the same way that stroke occurs in humans.
The team charted the death of neurons in the rat’s hippocampus from the blood deprivation, choosing the hippocampus because it is large in rodents and easy to visualize. It is also functionally similar to the human hippocampus, and is the center of learning and memory, which the scientists tested for improvements in behavior.
Once the cells died, a growth factor “cocktail” was injected into the ventricular space near the hippocampus, where a large number of stem cells were lying dormant. Their hope was that the growth factor would awaken the sleeping cells.
They were not disappointed.
Regrowth – and Recovery
The neurons started to regenerate, and kept on doing so until nearly 40 percent of them regrew. Even more important, this amount of growth enabled the stroke-induced rats to regain enough memory to navigate a complicated obstacle course.
The bottom line? The cocktail stirred the dormant stem cells to do what they did when the brain was first developing. The stem cells migrated to the area of damage and began to grow into new nerve cells, filling the gap left by the injury.
“They were doing exactly what we expect they would do during embr yogenesis,” Nakafuku says. “We’re just trying to get the stem cells to re-create the miracle that they do every time during development.”
Adapting the Research to People
As exciting as these findings are, there are many more hurdles before the findings can be adapted to humans. One essential task is determining which of the more than 100 thousand different types of cells involved in the central nervous system need to be replicated for each specific disease.
“Unlike diabetes, in which only one cell type is lost, nerve cell injuries often cause loss or damage to thousands of different types of cells,” Nakafuku explains. “It makes figuring out what goes wrong, which cells need replacement, and what to do to get them recovered, a daunting task.”
Still, even incremental improvements could help children with congenital brain disorders, Nakafuku says. His team has chosen these disorders as an area of focus for future research.
“For a child with Down syndrome, for example, maybe we could lessen the severity — not cure him, but supply some essential functions,” Nakafuku says. “Children’s brains are thought to be more amenable to stem cell therapy because they are more plastic and have more stem cells.”
So even this cautious researcher believes stem cells offer promise.
“Stem cells present one of the best hopes right now among many possible therapies— despite the difficulties for scientists and researchers, they offer a huge hope. But we are well aware of the gap between that huge hope and the difficult situations we encounter everyday.”
Which is why Nakafuku and his team focus on how the normal brain develops, to better understand what can go wrong. “If stem cells can do miracles, the key behind that is in the normal process of development,” he says. “Because that is exactly what stem cells do each time embryos and fetuses grow.”
