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Illustration of the human body showing the skeletal system, the lower part of the spine being highlighted in red to indicate the pain points. Courtesy of image: Michigan Engineering
ANN ARBOR – An injection of nanoparticles can prevent the immune system from overreacting to trauma, potentially preventing certain spinal cord injuries from causing paralysis.
The approach has been demonstrated in mice from the University of Michigan, nanoparticles enhancing healing by reprogramming aggressive immune cells – call it an "EpiPen" for trauma to the central nervous system, which includes the brain and spinal cord.
"In this work, we demonstrate that instead of overcoming an immune response, we can cooperate with the immune response to work for us to promote the therapeutic response," said Lonnie Shea, professor of biomedical engineering at Steven College. A. Goldstein.
Lonnie Shea. Image credit: Michigan Engineering
Trauma of all kinds triggers the body's immune response. During a normal injury, the immune cells infiltrate the damaged area and remove debris to initiate the regeneration process.
However, the central nervous system is usually isolated from the barrier of immune activity by the blood-brain barrier. A spinal cord injury breaks this barrier by letting in over-zealous immune cells that create too much inflammation for delicate nerve tissue. This leads to the rapid death of neurons, damage to the insulating sheaths around the nerve fibers that allow them to send signals and the formation of a scar that blocks the regeneration of nerve cells in the spinal cord.
All this contributes to the loss of function below the level of the injury. This spectrum includes everything from paralysis to loss of sensation in many of the 12,000 new SCI patients each year in the United States.
Previous attempts to compensate for the complications of this immune response included the injection of steroids such as methylprednisolone. This practice has been largely abandoned because it causes side effects such as sepsis, gastrointestinal bleeding and blood clots. Risks outweigh the benefits.
But now, U-M researchers have designed nanoparticles that intercept immune cells moving towards the spinal cord, diverting them from the wound. Those that reach the spinal cord have been modified to become more pro-regenerative.
Hopefully this technology could lead to new therapeutic strategies not only for patients with spinal cord injury, but also for those suffering from various inflammatory diseases.
Jonghyuck Park
Without drugs, the nanoparticles reprogram the immune cells with their physical characteristics: a size similar to that of cell debris and a negative charge facilitating the binding to immune cells. In theory, their non-pharmaceutical nature avoids undesirable side effects.
With fewer immune cells at the site of trauma, there is less inflammation and tissue damage. Secondly, the immune cells responsible for the lesion are less inflammatory and more able to support tissues that are trying to regenerate.
"Hopefully this technology could lead to new therapeutic strategies not only for patients with spinal cord injury, but also for those suffering from various inflammatory diseases," said Jonghyuck Park, a U-M researcher working with Shea.
Previous research has shown the success of nanoparticles to reduce trauma caused by West Nile virus and multiple sclerosis, for example.
"The immune system underlies autoimmune disease, cancer, trauma, regeneration – almost every major disease," said Shea. "The tools that can target immune cells and reprogram them to the desired response offer many options for treating or managing the disease."
The research, published in the latest issue of Proceedings of the National Academy of Sciences, was funded by the National Institutes of Health. Shea also holds the William and Valerie Hall Biomedical Engineering Chair and Professor of Chemical Engineering.
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