Stem cells conditioned with a modified form of tissue-type plasminogen activator (tPA), a drug commonly used to treat non-hemorrhagic stroke, appear to help promote motor recovery in rats with spinal cord injury, researchers suggest in Scientific Reports.
tPA is used to break up blood clots, allowing blood to more freely flow back into the brain following a stroke. But tPA is also a naturally occurring enzyme known to boost neuron growth and dampen inflammation. So the researchers used an enzymatically inactive form of tPA, still anti-inflammatory and pro-neuron growth but without effect on blood clotting, which could be a dangerous side effect in a person not having a stroke.
In a laboratory dish, the researchers added the modified tPA to neural progenitor cells — the precursors to neurons. They had generated these pre-neurons from induced pluripotent stem cells. After 15 minutes, the researchers transferred either tPA-conditioned or unconditioned neural progenitor cells to the injury site in a rat model of severe spinal cord injury.
Two months after treatment, the researchers found 2.5-fold more tPA-conditioned neural progenitor cells than unconditioned cells still present in the rats. What’s more, the tPA-conditioned cells had begun specializing into full-fledged neurons, with axons (branches) emerging from the site of transplantation and extending as far as four vertebrae away, a media release from University of California – San Diego explains.
That’s an unusual occurrence, according to Wendy Campana, PhD, professor in the Department of Anesthesiology and Program in Neuroscience.
“It was striking to see at two and four months the tremendous improvements in the ability of those progenitor cells to survive in the injury cavity,” she says, in the release. “Just keeping these cells alive has been very difficult in past studies.”
The rats with modified tPA demonstrated a three-fold increase in motor activity after 4 months, as measured using a scoring system that quantifies a combination of rat joint and limb movements, trunk stability, paw and tail positioning, stepping and coordination.
Pain is a special focus of Campana’s lab, and the team was initially most interested in that aspect of spinal cord injury treatment. They measure pain in rat models based on how they lift their front paws in response to added weights.
“The addition of tPA-treated neural precursors didn’t reduce pain in this model,” Campana adds. “But we also didn’t exacerbate it — and to not see increased pain is important safety information for clinical translation to improve motor outcomes. We also don’t want worsen the pain burden of patients living with spinal cord injuries.”
One limitation of this spinal cord injury model is that the rats don’t live long enough to truly recapitulate what for humans is a long-term condition, or long enough to measure potential changes in gene expression over time. But it is currently the best available non-human primate model for the human situation, Campana notes, in the release.
In future studies, Campana and her team plan to explore further what, exactly, modified tPA does to neural progenitor cells on a molecular level that stimulates their growth and allows them to help repair spinal cord injuries.
[Source(s): University of California – San Diego, EurekAlert]