Implanted Neural Stem Cell Grafts and Functionality in Spinal Cord Injuries

Researchers at the University of California San Diego School of Medicine report that they have successfully implanted specialized grafts of neural stem cells directly into spinal cord injuries in mice. They then documented how the grafts grew and filled the site of injury, mimicking the mice’s existing neuronal network.

Almost 18,000 people in the U.S. suffer spinal cord injuries (SCIs) every year and another 294,000 people live with an SCI which is usually involving diminished physical function (such as difficulty breathing or bladder control) or some degree of permanent paralysis. It has long been the ambition of scientists to restore lost functions due to SCIs using stem cells.

Previous to the new study, neural stem cell grafts being developed in labs were sort of a black box. Although earlier research had shown improved functioning in SCI animal models following neural stem cell grafts, scientists were not quite sure what was happening.

Scientists knew that damaged host axons grow extensively into injury sites and that graft neurons in turn extended large numbers of axons into the spinal cord. However, they had no idea what kind of activity was occurring inside the graft itself and didn’t know if host or graft axons were actually making functional connections or if they only looked like they could.

The research team took advantage of recent technological advances which will allow researchers to both stimulate and record activity of genetically and anatomically defined neuron populations using light rather than electricity. This ensured the team would know exactly which host and graft neurons were at play without having to worry about electric currents spreading through tissue and potentially showing misleading results.

The team discovered that even in the absence of a specific stimulus, graft neurons fired spontaneously in very distinct clusters of neurons with highly correlated activity which was much like in the neural networks of the normal spinal cord. When they stimulated regenerating axons coming from the mice’s brain, they discovered that some of the same spontaneously active clusters of graft neurons responded robustly which indicated that those networks receive functional synaptic connections from inputs that typically drive movement. Sensory stimuli such as a pinch or light touch also activated graft neurons.

This showed that the team could turn on spinal cord neurons below the site of injury through stimulating graft axons extending into those areas. Through putting all these results together, it turns out that neural stem cell grafts have a remarkable ability to self-assemble themselves into spinal cord-like neural networks that functionally integrate with the host nervous system. Following years of inference and speculation, the team showed directly that each of the building blocks of a neuronal relay across injuries to the spine are in fact functional.

The team is now working on several avenues in an effort to enhance the functional connectivity of stem cell grafts such as organizing the topology of grafts to mimic those of the normal spinal cord with scaffolds and using electrical stimulation to strengthen the synapses between graft neurons and host.

While it may still be years off for the perfect combination of stem cells, stimulation, rehabilitation and other interventions, people are living with spinal cord injuries now. Therefore, the team is currently working with regulatory authorities to move their stem cell graft approach into clinical trials as soon as possible. They anticipate that if everything goes well, they could have a therapy within the next 10 years.

To view the original scientific study click below

Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury.