Novel approach also shows promise for autoimmune diseases
The paralyzing damage in a spinal cord injury (SCI) is often caused by the enthusiastic immune response to the injury. NIBIB-funded engineers have developed nanoparticles that drive immune cells away from the spinal cord, allowing regeneration that restored spinal cord function in mice.
As in the brain, the spinal cord has a blood-brain barrier that protects delicate nerves from possible damage caused by various insults, including blocking the entry of immune cells to clear the remains of the injury.
When the spinal cord suffers a traumatic injury, the blood-brain barrier is damaged and the rapid influx of immune cells creates an environment that aims to rapidly shore up the injury, but also inhibits regenerative processes that can successfully rebuild and reconnect the delicate damaged nerves.
Now NIBIB recipient Lonnie Shea, Ph.D., Steven A Goldstein Collegiate Professor of Biomedical Engineering, and colleagues at the University of Michigan in Ann Arbor have developed a strategy that redirects many immune cells away from the injury while inducing those that reach SCI to shift to an anti-inflammatory profile, producing factors that promote a regenerative healing process, which can preserve function. The single strategy is reported in the July issue of the Proceedings of the National Academy of Sciences. 1.
“Although the immune response is trying to do its job, rushing to the site of a spinal cord injury,” explains David Rampulla, Ph.D., NIBIB program director in Drug and Biologics Delivery Systems and Devices, “the rapid removal of injured cells and repair of the damaged area by immune cells often results in a buildup of fibrotic tissue that essentially fills the wound with structural cells that are not functional neurons. Recognizing this, Michigan engineers have designed an approach that reduces immune cells at the site of spinal injury, while promoting further regeneration.”
The Michigan team designed nanoparticles that can be injected into the bloodstream directly after a spinal cord injury. Nanoparticles employ several simple mechanisms that allow them to reprogram immune cells: the nanoparticles mimic the small size of cellular debris, and therefore the immune cells get to work enveloping the nanoparticles. The nanoparticles are also negatively charged, making it easier to bind to positively charged immune cells. Immune cells that are redirected from the spinal cord are eventually sequestered in the spleen, which acts by filtering waste and recycling components of red and white blood cells.
Some cells escape the deflection of the nanoparticles, but overall there is a dramatic reduction in the number of immune cells entering the wound area. The lower number of immune cells causes the cells to switch from an inflammatory to a regenerative profile.
The team tested the nanoparticles in a mouse SCI model, where they observed a reduction in fibrosis and an increase in regenerative processes. Furthermore, in functional studies, mice receiving nanoparticle therapy showed improved locomotor function.
“We hope that these encouraging results may lead to a novel treatment for many of the 12,000 new spinal injury patients in the U.S. each year,” Shea says. “In addition, this nanoparticle technology may have applications in the treatment of a significant number of diseases caused by an immune response ranging from arthritis to sepsis.”
This study was supported by NIH grants R01EB005678 and R01EB013198 from the National Institute of Biomedical Imaging and Bioengineering.
