But if those critical V2a interneurons could be regenerated in an injured spine, the researchers wondered, perhaps the spinal cord could re-establish the connection and heal itself.
For the past three years, McDevitt and his team have been working to culture viable human V2a interneurons from pluripotent stem cells. The process, known as differentiation, attempts to replicate in the lab the natural development of neurons from undifferentiated stem cells in a human embryo.
Decades of research in developmental biology have provided clues to how genes in a developing embryo direct different proteins and other chemical factors to create all manner of specialized cells. The trouble is that most of the “recipes” for these chemical “cocktails” were derived from studying animal embryos.
“Obviously, for good reasons, we don’t do experiments on human embryos,” McDevitt said. “You have to take a leap of faith from the developmental biology knowledge we have from worms and flies and think about how we can apply that really important biological information to the human context.”
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After experimenting with round after round of chemical combinations, the researchers landed on a process that can now produce a sizable batch of human V2a interneurons in a little over two weeks. The first step was to inject the cells into the spinal cords of healthy mice and see if the cells survived. They did even better.
“Within two weeks, we saw a number of these cells extend their axons over long distances — five millimeters reliably, but some even longer than that,” McDevitt said, adding that the wiry cells are also making important connections. “Even though they’re mice, we see these human cells that appear to be connecting to other neurons.”
Does this mean we’re close to a human therapy using injections of healthy neurons to repair damaged spines? Not quite. Trials will first need to be run with injured mice before any human subjects can be tested. Plus, it’s entirely possible that V2a interneurons only fix very specific types of spinal injuries, or none at all. It might require the production of other spinal cord neurons, or a combination of several, to find the most effective treatment.
“At the most basic level, this work shows that we can successfully introduce a new type of spinal neuron made from human pluripotent stem cells,” McDevitt said. “I see it as a step in what’s probably going to be a much bigger effort by the field.”
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