Researchers Use Stroke Drug to Treat Spinal Cord Injury in Rats

Wednesday, December 18, 2019 - 14:48

Researchers from University of California have treated rats with spinal cord injuries through applying neural progenitor cells that had been pre-conditioned with a modified form of tPA, a drug commonly used to treat non-hemorrhagic stroke.

According to the Science Daily report, Yasuhiro Shiga, MD, PhD, and his supervisor, Wendy Campana, PhD, professor in the Department of Anesthesiology and Program in Neuroscience, could treat rats with spinal cord injuries with neural progenitor cells that had been pre-conditioned with a modified form of tPA.

The difference for those rats was this: Before delivering them into the spinal cord injury site, Shiga and Campana had conditioned stem cells with a modified form of tissue-type plasminogen activator (tPA), a drug commonly used to treat non-hemorrhagic stroke.

Based on the results published December 17, 2019 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, a special kind of stem cell that can be derived from a person's skin 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. According to Campana, that's unusual.

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 said.

The team next plans to dive into 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.


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