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John W. McDonald, M.D., Ph.D. an associate professor of neurology at the Johns Hopkins University School of Medicine and director of the International Center for Spinal Cord Injury at Kennedy Krieger Institute taps into the body’s own repair mechanisms in search of treatments for spine injury.
Stem cells allow us to address questions I’ve thought about forever. These are really exciting times for the repair of the nervous system, because we can move beyond mere correlation and get definitive answers.
Despite what I was taught in medical school, nervous system cells do divide and grow. Not all of them. But oligodendrocytes are the most prominent ones that do. If we were to follow newly born cells in an adult human brain for an hour, the majority of those cells would go on to become oligodendrocytes.
Injury and the consequence of injury disrupts the turning over of cells, basically because of reduced electrical activity, which oligodendrocytes depend on for survival and myelination.
I’m convinced that endogenous stem cells in the spinal cord—those naturally born there by the million, every hour, even in spinal cord injured adults—represent an important therapeutic target.
Through the transplantation work we’re doing in mice, we’re learning a lot about the natural environment of cells in the nervous system. For example, mouse embryonic stem cells have the innate mechanism to overcome physical and chemical barriers. Their presence changes the microenvironment enough so that endogenous cells are able to cross barriers such as scars. We are working on figuring how to activate the same cues that cause those microenvironment changes without actually transplanting stem cells.
The whole nervous system—all the signaling between cells—runs by electrical activity. We’re just now getting access to the imaging tools to be able to see and begin to understand it. If that ensemble of activity is disrupted by injury, what percent of connections remain, and how can we use what remains to recreate the orchestra?
“New imaging methods now are confirming earlier animal studies that as much as 30 percent of connections can still remain below the level of spinal cord injury, even in the severe injury scenarios. This realization—that we don’t need to cure the nervous system, we just need partial repair—is born out in people who’ve had bad spinal cord injuries who now can regain substantial function and even walk..
“Our strategy is to maximize the physical integrity of your body so it can meet a cure halfway when a cure comes. We discovered that we can make a great impact on an individual’s own spontaneous recovery by facilitating the body’s own micro-repair system.
“What we do in lab is geared toward understanding these mechanisms of microrepair. We already know that myelination and birth of oligodendrocytes are incredibly dependent on electrical activity.”
Our focus now is on figuring out how to empower a body’s own endogenous stem cells, and using embryonic stem cells as scientific tools of discovery.
--Interviewed by Maryalice Yakutchik