The Tabulae Paralytica contains single-cell and spatial atlases of injury to the spine
A Spinal-Cell Bioinfection Atlas using Machine-Learning Techniques: a Comprehensive Analyses of Biological Responses in Mice
The researchers examined sections of the spinal cord, sampled from 52 injured and uninjured mice at 1, 4, 7, 14, 30 and 60 days after injury. Their analysis looked at 18 experimental SCI conditions with different types of injury and severity. They used RNA-sequencing tools to explore how 482,825 cells responded to injury over time.
Like the brain, the spine is made of delicate tissue that is separated from the immune system by physical barriers. When the neck is damaged, the immune cells of the body start to attack it. This keeps the injury free of infectious agents but can cause more serious damage to the body. The influx peaks between 7 and 14 days after an injury.
The atlas was built with the help of machine- learning techniques, and used a variety of cell biology techniques. They described their work in a Nature paper and have made the entire atlas available on the internet.
The Effect of Injury on the Blood-Spinal Cord Barrier and the Arachnoid Barrier in Old Mice with a Gene-Expressed Virus
They also found that injury immediately impairs the function of cells that form the blood–spinal cord barrier and the arachnoid barrier — a protective membrane that covers the spinal cord.
Anderson says that the barriers form in young animals but are malfunctioning in old mice.
Older mice had more extensive neuronal loss and a bigger invasion of immune cells. Their ability to recover from SCI was also reduced, leading to functional impairments and paralysis.
The researchers used the atlas to design a therapy to promote wound repair in older mice. They used a virus to deliver genes programmed to express three growth factors — EGF, FGF2 and VEGF — to spinal-cord cells. These genes can increase the growth of cells that form the blood–spinal cord barrier.
The researchers say they have found proof of principle with their study, but caution that more work is needed before this approach could benefit people with similar injuries.
One key challenge will be controlling the duration of the gene therapy’s effects. Timothy O’Shea is a medical engineer at Boston University who says that they don’t want to be stimulating the response chronically.
It’s important to know what the best time to administer the treatments is. The kind of caveats that need to be worked out from a therapeutic standpoint are still there, says O’Shea.
