When people damage their spinal cords, a lot of the long-term consequences often stem from the body’s overreaction to the injury. That’s because the blood-brain barrier protecting the spinal cord becomes compromised and overly aggressive immune cells flood in. Now, a team from the University of Michigan has developed a way of using intravenously delivered nanoparticles to reprogram how these immune cells deal with spinal cord injuries once they reach the area of damage. The idea is to reduce inflammation and stimulate the cells to support tissue healing to achieve better outcomes. Moreover, a part of their technique is to steer only the modified immune cells toward the injury while flagging others to stay away.
The team’s research, so far only performed on laboratory mice, has shown that the nanoparticle approach leads to an improved concentration of immune cells, significantly less scarring, and improved locomotor function compared with a control group of mice.
“In this work, we demonstrate that instead of overcoming an immune response, we can co-opt the immune response to work for us to promote the therapeutic response,” said Lonnie Shea, one of the leaders of the research.
Here’s some details about the nanoparticles and the study results according to the abstract in Proceedings of the National Academy of Sciences:
In this study, i.v. administered poly(lactide-coglycolide) nanoparticles were internalized by circulating monocytes and neutrophils, reprogramming these cells based on their physicochemical properties and not by an active pharmaceutical ingredient, to exhibit altered biodistribution, gene expression, and function. Approximately 80% of nanoparticle-positive immune cells were observed within the injury, and, additionally, the overall accumulation of innate immune cells at the injury was reduced 4-fold, coinciding with down-regulated expression of proinflammatory factors and increased expression of antiinflammatory and proregenerative genes. Furthermore, nanoparticle administration induced macrophage polarization toward proregenerative phenotypes at the injury and markedly reduced both fibrotic and gliotic scarring 3-fold. Moreover, nanoparticle administration with the implanted multichannel bridge led to increased numbers of regenerating axons, increased myelination with about 40% of axons myelinated, and an enhanced locomotor function (score of 6 versus 3 for control group).
Study in Proceedings of the National Academy of Sciences: Intravascular innate immune cells reprogrammed via intravenous nanoparticles to promote functional recovery after spinal cord injury