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  4. Single-Cell Multi-omics Assessment of Spinal Cord Injury Blocking via Cerium-doped Upconversion Antioxidant Nanoenzymes

Single-Cell Multi-omics Assessment of Spinal Cord Injury Blocking via Cerium-doped Upconversion Antioxidant Nanoenzymes

Advanced Science, 2025 · DOI: 10.1002/advs.202412526 · Published: January 9, 2025

Spinal Cord InjuryNeurologyBiomedical

Simple Explanation

Spinal cord injury (SCI) is a serious condition that damages the central nervous system. This damage often leads to the breakdown of the myelin sheath, which is crucial for nerve function, due to the presence of harmful reactive oxygen species (ROS). This breakdown further hinders the recovery of function. To address this, researchers have developed a strategy called SETLSA, which involves both treating the injury and assessing its severity using cerium (Ce)-doped upconversion antioxidant nanoenzymes (Ce@UCNP-BCH). These nanoenzymes work by eliminating ROS at the injury site and dynamically monitoring the oxidative state during the repair process using a special luminescence signal. The study also used advanced single-cell sequencing techniques to understand how Ce@UCNP-BCH treatment affects the spinal cord tissue at a cellular level, revealing an increase in myelinating oligodendrocytes and higher expression of genes related to myelination, as well as the gene regulatory dynamics of remyelination after treatment.

Study Duration
Not specified
Participants
Adult mice (three groups)
Evidence Level
Level Not specified, Animal study

Key Findings

  • 1
    Ce@UCNP-BCH effectively facilitates the regeneration of spinal cord including myelin sheath, and promotes the functional recovery of SCI mice.
  • 2
    The study reveals a significant increase in myelinating oligodendrocytes, as well as higher expression of myelination-related genes.
  • 3
    The ETLSA strategy synergistically boosts ROS consumption through the superoxide dismutase (SOD)-related pathways after SOD-siRNA treatment.

Research Summary

The study introduces a SETLSA strategy for spinal cord injury (SCI) treatment based on cerium (Ce)-doped upconversion antioxidant nanoenzymes (Ce@UCNP-BCH). These nanoenzymes eliminate reactive oxygen species (ROS) and dynamically monitor oxidative stress via ratiometric luminescence. The research combines snATAC-seq and snRNA-seq to analyze the heterogeneity of spinal cord tissue after Ce@UCNP-BCH treatment. Key findings include increased myelinating oligodendrocytes and higher expression of myelination-related genes, revealing the gene regulatory dynamics of remyelination. The study demonstrates that the ETLSA strategy enhances ROS consumption through superoxide dismutase (SOD)-related pathways after SOD-siRNA treatment, suggesting a synergistic approach to promoting SCI repair by blocking and dynamically monitoring oxidative stress.

Practical Implications

Therapeutic Development

The Ce@UCNP-BCH nanoenzymes offer a promising therapeutic avenue for spinal cord injury by simultaneously reducing oxidative stress and promoting tissue regeneration.

Diagnostic Potential

The ratiometric luminescence signal enables real-time monitoring of the oxidative state during SCI repair, facilitating personalized treatment strategies.

Mechanistic Understanding

The single-cell multi-omics analysis provides deeper insights into the cellular and molecular mechanisms underlying SCI recovery, potentially leading to new therapeutic targets.

Study Limitations

  • 1
    The optimal delivery mode and long-term adverse effects of Ce@UCNP-BCH were not determined.
  • 2
    Further optimization of the nanoparticle structure and monomer ratio is required to enhance diffusion and improve delivery efficiency.
  • 3
    The study primarily focuses on the cell nucleus, which means that mRNA information in the cytoplasm is not captured.

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