A recent spinal injury study could lead to new stem cell therapies after rare neurons were found to reconnect damaged spinal circuits and trigger leg muscle activity.
Scientists transplanted neural progenitor cells, early-stage cells that can develop into different types of nerve cell, into injured spinal cords in animal models and examined how the transplanted cells connected to surrounding nerve networks.
The research examined how graft-derived neurons connected to spinal motor circuits that control the hind limbs.
When a small subset of these transplanted neurons was experimentally activated, the animals’ leg muscles responded, providing evidence that the grafted cells had become part of the spinal cord’s motor circuitry.
Jennifer Dulin, assistant professor of biology at Texas A&M University and the study’s senior author, said: “Imagine an electrical circuit with a battery on one end and a light bulb on the other.
“If the wires between them are disconnected, the light bulb won’t turn on. A spinal cord injury breaks that circuit.
“What we’re trying to do is place new cells into the middle so they can reconnect the pathway and allow signals to flow again.”
The team found that these key interneurons, nerve cells that act as links between other neurons, were relatively rare in the transplanted cell population.
Leg muscle responses were seen in about 20 to 30 per cent of animals. Dulin said even that level is significant.
“This is meaningful because it shows that the potential to re-create these walking neural circuits is there,” Dulin said.
“The next step is understanding why some animals respond to the treatment and others don’t.”
The findings could help guide future regenerative therapies by showing which specific neurons may need to be enriched in transplanted cell populations.
The research also points to another factor that may influence recovery: rehabilitation.
Newly transplanted neurons are immature and must adapt to the spinal cord’s environment, Dulin said, a process that depends on activity.
“We’re essentially putting newborn neurons into the spinal cord, and they don’t have any experience yet,” she said
. “Just like babies learn by interacting with their environment and practising movements, these transplanted neurons need activity to learn how to function within the circuit.”
Pairing targeted cell therapies with activity-based rehabilitation could therefore be essential in helping transplanted neurons integrate into the body’s existing motor networks.
“This kind of basic biology research is critically needed in order to develop new therapies,” Dulin said.
“For decades in the field of spinal cord injury, we’ve just been testing treatments without really understanding how they work.
“We’re entering a new era where we have amazing tools to really study the effects of a treatment on an individual cellular level.
“These kinds of studies are critical to paving the way for effective human treatments.”
