A team of researchers from the Gladstone Institutes announces the creation of what they call V2a interneurons, which are created from human stem cells and transmit signals in the spinal cord to help control movement.
When the researchers implanted these cells into the spinal cords of mice, they sprouted and integrated with existing cells. This action gives the researchers hope that the V2a interneurons may someday help repair spinal cord injuries (SCIs).
V2a interneurons relay signals from the brain to the spinal cord, where they ultimately connect with motor neurons that project out to the arms and legs. They project up and down the spinal cord to initiate and coordinate muscle movement, as well as breathing. Damage to V2a interneurons can sever connections between the brain and the limbs, which contributes to paralysis following spinal cord injuries.
“Interneurons can reroute after spinal cord injuries, which makes them a promising therapeutic target,” says senior author Todd McDevitt, PhD, a senior investigator at Gladstone, in a media release from Gladstone Institutes. “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.”
In their study, published in the Proceedings of the National Academy of Sciences, the researchers produced V2a interneurons from human stem cells for the first time. They identified a cocktail of chemicals that gradually coaxed the stem cells to develop from spinal cord progenitor cells to the desired V2a interneurons. By adjusting the amounts of three of the chemicals and when each one was added, the scientists refined their recipe to create large amounts of V2a interneurons from stem cells, the release explains.
“Our main challenge was to find the right timing and concentration of the signaling molecules that would yield V2a interneurons instead of other neuronal cell types, such as motor neurons,” states first author Jessica Butts, a graduate student in the McDevitt lab. “We used our knowledge of how the spinal cord develops to identify the right combination of chemicals and to improve our procedure to give us the highest concentration of V2a interneurons.”
Then, in collaboration with Linda Noble, PhD, at the University of California, San Francisco, the researchers implanted the V2a interneurons into the spinal cords of healthy mice. The cells matured and integrated with the existing spinal cord cells. The mice moved normally after the implantation and showed no signs of impairment.
“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,” says co-author Dylan McCreedy, PhD, a postdoctoral scholar at Gladstone, per the release.
The researchers state that their next step will be to transplant the cells into mice with spinal cord injuries to see if the V2a interneurons can help restore movement. In addition, they are also interested in exploring the potential of these cells in models of neurodegenerative movement disorders such as ALS.
[Source(s): Gladstone Institutes, Science Daily]