Cell Type Counts in Spinal Therapy

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Neuron bridge: Two different astrocyte populations grown from the same stem cell line have different effects when injected into the injured spinal cords of rats. Above, an injury site injected with one type of astrocyte (red) is full of new nerve fibers that successfully bridge the injury. Below, a similar injury site injected with a different type of astrocyte (red) shows fewer nerve fibers (green) that fail to bridge the gap. Credit: Stephen Davies/University of Colorado

Every three days after surgery, the researchers tested the rats' ability to walk across a horizontal ladder. They found that the rats that received GDAbmp injections quickly recovered motor skills and were able to walk across the ladder as well as they could before the surgery. By contrast, the rats injected with GDAcntf or with naïve stem cells showed no statistically significant recovery, similar to rats that received no injection at all.

Images of each injury site after cell injections showed that GDAbmp astrocytes promoted the regeneration of severed nerve fibers across spinal cord injuries while the GDAcntf and naïve stem cells did not.

In addition, Davies' colleague and wife Jeannette Davies discovered that rats with injected GDAcntf astrocytes were much more sensitive to pain than rats with GDAbmp astrocytes. Furthermore, in histological samples, the team found that rats with GDAcntf exhibited sprouting of nerve fibers associated with neuropathic pain, whereas rats with GDAbmp did not show such sprouting.

"So far, these [GDAbmp astrocytes] are the gold standard astrocytes that have been discovered," says Davies. "Not only do they not promote neuropathic pain, but they have robust regeneration of neurons, and [they lead to] locomotor recovery in two to three weeks."

Davies says manipulating stem cells before transplanting them into injured sites may have beneficial effects not just for repairing spinal cords, but also for treating injuries in other parts of the body. For now, he and his team are exploring methods to make GDAbmp for humans, either from embryonic stem cells or from adult stem cells, with a view toward transplanting these cells into humans in clinical trials in the next two or three years.