Intravascular innate immune cells reprogrammed via intravenous nanoparticles to promote functional recovery after spinal cord injury

PNAS, 2019 · DOI: 10.1073/pnas.1820276116 · Published: July 8, 2019

Simple Explanation

Traumatic spinal cord injury (SCI) leads to inflammation and tissue damage, impairing function. This study uses nanoparticles to target and reprogram circulating immune cells, reducing inflammation and promoting a pro-regenerative environment in the injured spinal cord. The nanoparticles, made of poly(lactide-coglycolide) (PLG), are administered intravenously and internalized by monocytes and neutrophils. This reprograms these immune cells to alter their behavior without using an active pharmaceutical ingredient. This approach leads to decreased tissue degeneration, increased expression of regeneration-associated genes, enhanced axon regeneration and myelination, and improved functional recovery after SCI.

Study Duration

84 days

Participants

C57/BL6 female mice (6–8 wk old, 20–25 g)

Evidence Level

Not specified

Key Findings

1
Intravenously administered nanoparticles are internalized by circulating monocytes and neutrophils, reprogramming these cells based on their physicochemical properties.
2
Nanoparticle administration reduces the overall accumulation of innate immune cells at the injury site and down-regulates the expression of proinflammatory factors while increasing the expression of antiinflammatory and proregenerative genes.
3
Nanoparticle administration induces macrophage polarization toward proregenerative phenotypes at the injury, reducing both fibrotic and gliotic scarring, and leads to increased numbers of regenerating axons and enhanced locomotor function.

Research Summary

This study investigates the potential for reprogramming circulating innate immune cells through nanoparticle administration to enhance functional regeneration following SCI. The nanoparticles (500 nm diameter, zeta potential < −30 mV) were administered intravenously daily for 7 days immediately after SCI, leading to altered biodistribution, gene expression, and function of immune cells. The results demonstrate that nanoparticles limit acute inflammation and tissue destruction, creating a proregenerative microenvironment that supports regeneration and functional recovery after SCI.

Practical Implications

Therapeutic Potential for SCI

Nanoparticles offer a new therapeutic avenue for spinal cord injury by modulating the immune response and promoting tissue regeneration.

Applications to Other Inflammatory Diseases

The nanoparticle-based approach may be applicable to other inflammatory diseases beyond SCI.

Safe and Readily Available Treatment

The nanoparticles are made of FDA-approved materials, stable at room temperature, and do not contain an active pharmaceutical ingredient, facilitating immediate i.v. administration.

Study Limitations

1
The study uses a lateral hemisection SCI model in mice, which may not fully represent the complexity of human SCI.
2
The long-term effects of nanoparticle administration beyond 84 days were not investigated.
3
The specific mechanisms by which nanoparticles reprogram immune cells require further investigation.

Your Feedback

Was this summary helpful?

Back to Immunology