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  4. Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury

Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury

Nature Communications, 2023 · DOI: 10.1038/s41467-023-40513-5 · Published: August 7, 2023

Spinal Cord InjuryNeurologyBioinformatics

Simple Explanation

Spinal cord injury (SCI) can lead to permanent motor and sensory dysfunction. This study used single-cell transcriptomics to understand cellular responses in rhesus monkeys with complete thoracic SCI. The researchers found that cells in distal lumbar tissue were severely impacted, leading to degenerative microenvironments. These environments were characterized by activated microglia and oligodendrocytes, and an increased proportion of inhibitory interneurons. Implanting a scaffold at the injury site improved the microenvironment by regulating glial cells and fibroblasts. It also remodeled spared lumbar tissues by reducing inhibitory neuron proportion and improving phagocytosis and myelination.

Study Duration
6 Months
Participants
12 adult female rhesus monkeys
Evidence Level
Not specified

Key Findings

  • 1
    Distal lumbar tissue cells were severely impacted, leading to degenerative microenvironments characterized by disease-associated microglia and oligodendrocytes activation alongside increased inhibitory interneurons proportion following SCI.
  • 2
    Functional collagen scaffold implantation in the injury sites could remodel the microenvironment of the injury sites and the lumbar tissues, highlighting the potential of scaffold-based treatment strategies for repairing SCI.
  • 3
    Intense interactions between different cell subtypes play important roles in pathological changes in proximal regions after spinal cord injury.

Research Summary

This study constructed a cell atlas of different regions in the injured spinal cord of rhesus monkey from the acute to chronic phases, depicting the unique molecular heterogeneity and the spatio-temporal dynamics of multiple cell types. The atlas revealed that cells in the distal lumbar tissues below the lesion were also affected and generated a degenerative microenvironment with upregulated genes related to cellular stress, phagocytosis, and autophagy. Functional scaffold implantation could improve the microenvironment of both the lesion sites and the spared lumbar, rescue the dysfunction of neurons below the lesion, and mitigate the increase of inhibitory neurons induced by SCI.

Practical Implications

Therapeutic Targets

Identifies potential therapeutic targets below the lesion for SCI repair, focusing on cellular stress, phagocytosis, and autophagy.

Scaffold-Based Treatment

Emphasizes the potential of scaffold-based treatment approaches targeting heterogeneous microenvironments to improve outcomes after SCI.

Microenvironment Remediation

Highlights the importance of microglial-mediated debris phagocytosis and lipid recycling in microenvironment remediation in the distal lumbar.

Study Limitations

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