Scientists make stem cell-derived nerve cells damaged in spinal cord injury

The human spinal cord is an information highway that relays movement-related instructions from the brain to the rest of the body and sensory information from the body back to the brain. What keeps this highway flowing is a long tube of nerve cells and support cells bundled together within the spine.

When the spinal cord is injured, the nerve cells are damaged and can die – cutting off the flow of information to and from the brain. As a result, patients experience partial or complete paralysis and loss of sensation depending on the extent of their injury.

Unlike lizards which can grow back lost tails, the spinal cord cannot robustly regenerate damaged nerve cells and recreate lost connections. Because of this, scientists are looking to stem cells for potential solutions that can rebuild injured spines.

Making spinal nerve cells from stem cells

Yesterday, scientists from the Gladstone Institutes reported that they used human pluripotent stem cells to create a type of nerve cell that’s damaged in spinal cord injury. Their findings offer a new potential stem cell-based strategy for restoring movement in patients with spinal cord injury. The study was led by Gladstone Senior Investigator Dr. Todd McDevitt, a CIRM Research Leadership awardee, and was published in the journal Proceedings of the National Academy of Sciences.

The type of nerve cell they generated is called a spinal interneuron. These are specialized nerve cells in the spinal cord that act as middlemen – transporting signals between sensory neurons that connect to the brain to the movement-related, or motor, neurons that connect to muscles. Different types of interneurons exist in the brain and spinal cord, but the Gladstone team specifically created V2a interneurons, which are important for controlling movement.

V2a interneurons extend long distances in the spinal cord. Injuries to the spine can damage these important cells, severing the connection between the brain and the body. In a Gladstone news release, Todd McDevitt explained why his lab is particularly interested in making these cells to treat spinal cord injury.

Todd McDevitt, Gladstone Institutes

“Interneurons can reroute after spinal cord injuries, which makes them a promising therapeutic target. Our goal is to rewire the impaired circuitry by replacing damaged interneurons to create new pathways for signal transmission around the site of the injury.”

 

Transplanting nerve cells into the spines of mice

After creating V2a interneurons from human stem cells using a cocktail of chemicals in the lab, the team tested whether these interneurons could be successfully transplanted into the spinal cords of normal mice. Not only did the interneurons survive, they also set up shop by making connections with other nerve cells in the spinal cord. The mice that received the transplanted cells didn’t show differences in their movement suggesting that the transplanted cells don’t cause abnormalities in motor function.

Co-author on the paper, Dylan McCreedy, described how the transplanted stem cell-derived cells behaved like developing V2a interneurons in the spine.

“We were very encouraged to see that the transplanted cells sprouted long distances in both directions—a key characteristic of V2a interneurons—and that they started to connect with the relevant host neurons.”

Todd McDevitt (right), Jessica Butts (center) and Dylan McCreedy (left) created a special type of neuron from human stem cells that could potentially repair spinal cord injuries. (Photo: Chris Goodfellow, Gladstone)

A new clinical strategy?

Looking forward, the Gladstone team plans to test whether these V2a interneurons can improve movement in mice with spinal cord injury. If results look promising in mice, this strategy of transplanting V2a interneurons could be translated into human clinic trials although much more time and research are needed to get there.

Trials testing stem cell-based treatments for spinal cord injury are already ongoing. Many of them involve transplanting progenitor cells that develop into the different types of cells in the spine, including nerve and support cells. These progenitor cells are also thought to secrete important growth factors that help regenerate damaged tissue in the spine.

CIRM is funding one such clinical trial sponsored by Asterias Biotherapeutics. The company is transplanting oligodendrocyte progenitor cells (which make nerve support cells called oligodendrocytes) into patients with severe spinal cord injuries in their neck. The trial has reported encouraging preliminary results in all six patients that received a dose of 10 million cells. You can read more about this trial here.

What the Gladstone study offers is a different stem cell-based strategy for treating spinal cord injury – one that produces a specific type of spinal nerve cell that can reestablish important connections in the spinal cord essential for movement.

For more on this study, watch the Gladstone’s video abstract “Discovery Offers New Hope to Repair Spinal Cord.


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How stimulating! A new way to repair broken bones

For those of us who live in earthquake country the recent devastating quakes in Nepal are a reminder, as if we needed one, of the danger and damage these temblors can cause. Many of those injured in the quake suffered severe bone injuries – broken legs, crushed limbs etc. Repairing those injuries is going to take time and expert medical care. But now a new discovery is opening up the possibility of repairing injuries like this, even regenerating the broken bones, in a more efficient and effective way.

shutterstock_18578173A study published in Scientific Reports  shows that it is possible to regrow bone tissue using protein signals from stem cells. Even more importantly is that this new bone tissue seems to be just as effective, in terms of the quantity and quality of the bone created, as the current methods.

In a news release senior author Todd McDevitt, Ph.D., said this shows we might not even need whole stem cells to regenerate damaged tissue:

“This proof-of-principle work establishes a novel bone formation therapy that exploits the regenerative potential of stem cells. With this technique we can produce new tissue that is completely stem cell-derived and that performs similarly with the gold standard in the field.”

McDevitt – who is now at the Gladstone Institutes thanks to a research leadership award from CIRM  – extracted the proteins that stem cells produce to help regenerate damaged tissues. They then isolated the particular factors they needed to help regenerate bones, in this case bone morphogenetic protein or BMP. That BMP was then transplanted into mice to stimulate bone growth. And it worked.

While this compares favorably to current methods of regenerating or repairing damaged bones it has a few advantages. Current methods rely on getting bones from cadavers and grinding them up to get the growth factors needed to stimulate bone growth. But bones from cadavers can often be in short supply and the quality is highly variable.

As McDevitt says:

“These limitations motivate the need for more consistent and reproducible source material for tissue regeneration. As a renewable resource that is both scalable and consistent in manufacturing, pluripotent stem cells are an ideal solution.”

He says the next step is to build on this research, and try to find ways to make this method even more efficient. If he succeeds he says it could open up new ways of treating devastating injuries such as those sustained by soldiers in battle, or by earthquake victims.