An injection of nanoparticles for spinal cord lesions



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Researchers at the University of Michigan have used the injection of nanopaticles to prevent the body's immune cells from altering the healing of the injured brain and spine. They call it an "EpiPen" or emergency relief medication for the brain and spinal cord when they are suffering from trauma.

Magnetic resonance imaging of the human shows a fracture and compresses the spine. Image Credit: SORANAT7 / Shutterstock

Magnetic resonance imaging of the human shows a fracture and compresses the spine. Image Credit: SORANAT7 / Shutterstock

The study titled "Intravascular Innate Immune Cells Reprogrammed via Intravenous Nanoparticles to Promote Functional Recovery After Spinal Cord Injury" was published in the latest issue of Proceedings of the National Academy of Sciences.

PLG multichannel bridge model and SCI half-section.PLG multichannel bridge model and SCI half-section.

Lonnie Shea, Associate Professor of Biomedical Engineering at Steven A. Goldstein College, William and Valerie Hall Chair of Biomedical Engineering and Professor of Chemical Engineering, said in the release the lead author of the study: Overcoming an Immune Response we can cooperate with the immune response to work for us to promote the therapeutic response. "

The researchers explain that when there is a trauma of any kind, there is an overload of the immune system that squeezes around the injured area to remove debris and dead cells. This allows the remaining tissues to heal and start the regeneration and repair process. When the lesion occurs in the central nervous system or in the brain and spinal cord, there is a movement of immune cells that are generally not allowed in the CNS normally because of the blood-brain barrier.

The spinal cord injury breaks the barrier and allows the immune cells to penetrate inside. This leads to an overactive immune activity that leads to inflammation and causes more damage to the nerve tissues of the spinal cord that are not accustomed to such activity. The first to be damaged are the sheaths surrounding the nerves that help them transmit the signals. This leads to scar development that is detrimental to the regeneration and repair process, the researchers explain.

As a result, all functions below the injury level are lost. It can be muscle weakness, loss of sensation or paralysis. In the United States, there are 12,000 people every year who have spinal cord injuries, the researchers write.

In order to reduce the inflammatory responses of the immune cells to the site of the lesion, the treatment previously consisted of injecting steroids, such as methylprednisolone. This can help stop inflammation, but presents a host of problems and risks, including bleeding from the gastrointestinal tract, blood clots, sepsis or infections.

To address this problem, researchers have developed nanoparticles capable of interrupting the movement of immune cells to the site of the lesion and redirecting them elsewhere to protect the site of the lesion. It can help the spinal cord heal and regenerate, writes the team.

These nanoparticles are just that: nanoparticles without any medicine. In fact, they act as decoys and appear as cellular debris from the injury. In addition, they have a negative charge that allows the immune cells to bind to them. The bound immune cells are thus rid of the wound site.

The researchers explain that the "non-pharmaceutical" nature of the nanoparticles makes them theoretically free of side effects. In this way, unwanted immune cells are eliminated and some that reach the site help the regeneration process, the researchers write.

The team wrote that it uses "poly (lactide-coglycolide) nanoparticles". She explains that these nanoparticles have been "internalized by circulating monocytes and neutrophils". After that, the immune cells were reprogrammed on the basis of their physicochemical properties, an active pharmaceutical ingredient. They explain that this linkage "alters the biodistribution, the gene expression and the function" of the cells. In their experiments, they noted that there was a four-fold reduction in the "overall accumulation of innate immune cells to injury".

In addition, there were other responses such as reducing "proinflammatory factor" formation, increasing "ana-inflammatory factors" on the site and stimulating genes that promote healing and regeneration. . After injection of the nanoparticles, the myelin sheath is regenerated about 40% around the axons of the neurons, the team wrote. This has resulted in movement and improvement function in laboratory animals.

According to Jonghyuck Park, co-author, "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." Shea explained well. added: "The immune system is at the root of autoimmune diseases, cancer, trauma, regeneration – almost all major diseases.The tools that can target immune cells and reprogram them according to the desired response offer many possibilities for treatment or management of the disease. "The possibilities could be explored regarding the West Nile virus and the trauma induced by multiple sclerosis, speculates the team.

The study was funded by the National Institutes of Health.

Source:

Journal reference:

Jonghyuck Park, Zhang Yining, Eiji Saito, Steve J. Gurczynski, B. Bethany, Brian J. Cummings, Anderson Aileen, Lonnie D. Shea, & # 39;Intravascular innate immune cells reprogrammed via intravenous nanoparticles to promote functional recovery after spinal cord injury& # 39; Proceedings of the National Academy of Sciences, July 2019, 201820276; DOI: 10.1073 / pnas.1820276116, https://www.pnas.org/content/early/2019/07/02/1820276116

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