Scientists at the Gladstone Institutes created a special type of neuron from human stem cells that could potentially repair spinal-cord injuries. These cells, called V2a interneurons, transmit indicators in the spinal cord to help control movement. When the researchers transplanted the cells into mouse spinal cords, the interneurons sprouted and integrated with existing cells.
V2a interneurons relay signals from the brain towards the spinal cord, where they ultimately connect with motor neurons that will project out to the arms and legs. The interneurons cover lengthy distances, projecting up and down the spinal cord to initiate plus coordinate muscle movement, as well as breathing. Damage to V2a interneurons can sever connections between the brain and the limbs, which usually contributes to paralysis following spinal cord injuries.
“Interneurons can reroute after spinal cord injuries, which makes them a good therapeutic target, ” said senior author Todd McDevitt, PhD, a senior investigator at Gladstone. “Our objective is to rewire the impaired circuitry by replacing broken interneurons to create new pathways for signal transmission across the site of the injury. ”
Several medical trials are testing cell replacement therapies to treat spinal-cord injuries. Most of these trials involve stem cell-derived neural progenitor cells, which can turn into several different types of brain or spinal-cord cells, or oligodendrocyte progenitor cells, which create the particular myelin sheaths that insulate and protect nerve tissues. However , these approaches either do not attempt or are unable to reliably produce the specific types of adult spinal cord neurons, for example V2a interneurons, that project long distances and restore the spinal cord.
In the current study, published within the Proceedings of the National Academy of Sciences , the researchers produced V2a interneurons from individual stem cells for the first time. They identified a cocktail associated with chemicals that gradually coaxed the stem cells to build up from spinal cord progenitor cells to the desired V2a interneurons. By adjusting the amounts of three of the chemicals so when each one was added, the scientists refined their formula to create large amounts of V2a interneurons from stem tissue.
“Our main challenge was to find the correct timing and concentration of the signaling molecules that would produce V2a interneurons instead of other neuronal cell types, like motor neurons, ” said first author Jessica Butts, a graduate student in the McDevitt lab. “We utilized our knowledge of how the spinal cord develops to identify the right mixture of chemicals and to improve our procedure to give us the best concentration of V2a interneurons. ”
Doing work in collaboration with Linda Noble, PhD, at the University associated with California, San Francisco (UCSF), the scientists transplanted the V2a interneurons into the spinal cords of healthy mice. Within their new environment, the cells matured appropriately and integrated along with existing spinal cord cells. Importantly, the mice moved usually after the interneurons were transplanted and showed no indications of impairment.
“We were very encouraged to find out that the transplanted cells sprouted long distances in both instructions — a key characteristic of V2a interneurons — and they started to connect with the relevant host neurons, ” said co-author Dylan McCreedy, PhD, a postdoctoral scholar at Gladstone.
The researchers say their next step would be to transplant the cells into mice with spinal cord injuries to find out if the V2a interneurons can help to restore movement after harm has occurred. They are also interested in exploring the potential role of those cells in models of neurodegenerative movement disorders such as amyloid lateral sclerosis.
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