A new facet of the old medicine

Researchers from the University of California, San Diego have developed a way to prepare stem cells before transplantation to rats for the treatment of spinal cord injuries. Neural progenitor cells of neurons were treated with a modified form of tissue plasminogen activator (tPA), a drug commonly used to treat non-hemorrhagic stroke. tPA dissolves blood clots, restoring blood supply to the damaged part of the brain. But it also stimulates the growth of neurons and reduces inflammation. The researchers used an enzymatically inactive form of tPA, preserving the anti-inflammatory and proneurogenic effects without affecting blood clotting. The precursors of neurons were created from induced pluripotent stem cells derived from human skin cells.

After 15 minutes, the researchers injected tPA-treated and control neural progenitor cells into the injury site of rat models of severe spinal cord injury.

Two months after treatment, the researchers found 2.5 times more tPA-treated neural progenitor cells than untreated cells still present in rats. Moreover, tPA-conditioned cells began to turn into full-fledged neurons with axons coming from the transplant site and stretching up to four vertebrae.

Microscopy of the damaged spinal cord of rats. On the right is a large number of axons originating from nerve progenitor cells that appear when the cells are pre–conditioned with modified tPA. On the left is the spinal cord of control rats that received untreated stem cells.

After four months, the rats that received stem cells with tPA had a threefold increase in motor activity. It was measured using a well-established evaluation system that quantifies the combination of movements of the joints of rats and limbs, body stability, the location of paws and tail, steps and coordination.

The group also became interested in the intensity of pain after treatment of spinal cord injuries. They measured pain in rat models based on how they lift their front paws in response to weight addition.

Transplantation of tPA-treated stem cells did not reduce the pain, but did not worsen it either – in this case, such a result is important information on the safety of the method for its future introduction into clinical practice.

One of the limitations of the rat model of spinal cord injury is the short life of this animal species – it is not enough to assess the long-term effect and potential changes in gene expression over time.

Currently, there is no FDA-approved method of treating spinal cord injuries with stem cells.

Article by Y.Shiga et al. Tissue-type plasminogen activator-primed human iPSC-derived neural progenitor cells promote motor recovery after severe spinal cord injury published in the journal Scientific Reports.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on UC San Diego News Center: Stroke Drug Boosts Stem Cell Therapy for Spinal Cord Injury in Rats.