Neural stem cell transplants hold promise for spinal cord injury

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Cell Stem Cell: Neural stem cell transplants hold promise for spinal cord injury

Using stem cells to restore function lost through spinal cord injury has long been an ambition of scientists and doctors.

Nearly 18,000 people in the United States suffer from spinal cord injuries each year, and another 294,000 have some degree of permanent paralysis or reduced physical function, such as bladder control or difficulty breathing.

In a new study, researchers from the University of California, San Diego School of Medicine report that they successfully implanted highly specialized grafts of neural stem cells directly into the site of spinal cord injury in mice and then recorded how the grafts did.

Grows and fills the injury site and integrates with the existing neuronal network in these mice. Related research results were recently published in the journal Cell Stem Cell with the title “Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury”.

Image via Cell Stem Cell, 2020, doi:10.1016/j.stem.2020.07.007.

Before this study, neural stem cell transplants

developed in the lab were a bit of a black box, said first author Mark H. Tuszynski, PhD, professor of neuroscience and director of the UC San Diego School of Medicine’s Translational Neuroscience Institute .

While previous studies have shown improved function in animal models of spinal cord injury after neural stem cell transplantation, scientists didn’t know exactly what happened.

“Injured host axons grow extensively [to the injury site], and the transplanted neurons in turn extend large numbers of axons into the spinal cord, but we don’t know exactly what’s going on inside the graft itself,” Ceto said. … We don’t know if host axons and graft axons are actually making functional connections, or if they just look like they might be.” Ceto, Tuszynski and colleagues took advantage of recent technological advancements to be able to use light instead of electricity Stimulate and record the activity of genetically This ensures they know exactly which host and transplant neurons are at work, without having to worry about the current spreading through the tissue giving potentially misleading results.

The researchers found that even in the absence of a specific stimulus, the transplanted neurons spontaneously fired in distinct clusters of neurons with highly correlated activity, just as in the neural network of the normal spinal cord.

When stimulating regenerating axons from the mouse brain, they found that some of the same clusters of spontaneously active transplanted neurons responded robustly, suggesting that these neural networks gain functional synapses from inputs that normally drive movement connect.

Sensory stimuli, such as light touch and pinch, also activated the transplanted neurons. “We found that we could activate spinal cord neurons below the injury site by stimulating the graft axons that extended into these areas,” Ceto said. Putting all these results together shows that neural stem cells

The grafts were able to self-assemble into spinal cord-like neural networks that were functionally integrated with the host nervous system. After years of guesswork and inference, we have directly confirmed that every axon of neurotransmission across SCI is actually functional.

says his team is now investigating several ways to enhance the functional connectivity of stem cell grafts, such as assembling the graft topology with scaffolds to mimic the topology of the normal spinal cord, and using electrical stimulation to strengthen the host and graft The synapses between neurons.

“While the perfect combination of stem cells, stimulation, rehabilitation and other interventions may be years away, patients are suffering from spinal cord injuries today.

Therefore, we are currently working with regulatory authorities to advance our stem cell transplantation approach to clinical trials as quickly as possible . If all goes well, we may have a cure within a decade. “

References:

1.Steven Ceto et al. Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury. Cell Stem Cell, 2020, doi:10.1016/j.stem.2020.07.007.

2.Implanted neural stem cell grafts show functionality in spinal cord injuries

Cell Stem Cell: Neural stem cell transplants hold promise for spinal cord injury

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