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  4. Multichannel bridges and NSC synergize to enhance axon regeneration, myelination, synaptic reconnection, and recovery after SCI

Multichannel bridges and NSC synergize to enhance axon regeneration, myelination, synaptic reconnection, and recovery after SCI

Not specified, 2023 · DOI: https://doi.org/10.21203/rs.3.rs-3044426/v1 · Published: July 19, 2023

Spinal Cord InjuryRegenerative Medicine

Simple Explanation

This study investigates a combination therapy for spinal cord injury (SCI) using a multichannel bridge made of poly(lactide-co-glycolide) (PLG) and human neural stem cells (hNSC). The PLG bridge provides structural support and reduces inflammation, while hNSCs promote axon myelination. The researchers found that culturing hNSCs on a PLG scaffold encourages them to become oligodendrocytes, which are cells that produce myelin. In live animals, implanting the PLG bridge followed by hNSC transplantation led to the migration of hNSCs into the bridge channels. These hNSCs then developed into myelin-producing oligodendrocytes and synaptically integrated neurons. This combination therapy significantly improved locomotor recovery compared to control groups or hNSC transplant alone.

Study Duration
24 Weeks
Participants
Mice (C57BL/6, Rag1, CRYM-ZsGreen1 transgenic, EMX1:ROSA-CRYM-RFP)
Evidence Level
Not specified

Key Findings

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    PLG bridge implantation modulates the cellular immune response in vivo by prolonging the macrophage/microglial response.
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    hNSC culture on PLG substrate in the presence or absence of immune factors enhances oligodendroglial and suppresses astroglial lineage selection.
  • 3
    hNSC transplantation enhances axonal regeneration and remyelination in the PLG bridge.

Research Summary

This study demonstrates that a combination of acute PLG bridge implantation and chronic hNSC transplantation enhances neurorepair after spinal cord injury (SCI). The PLG bridge provides a permissive environment for axonal regeneration, while hNSCs differentiate into myelinating oligodendrocytes and synaptically integrated neurons, leading to improved locomotor recovery. The combination therapy promoted the re-establishment of synaptic neural circuitry between the brain and neuromuscular junction after SCI.

Practical Implications

Therapeutic Strategy

A temporally layered approach using acute bridge implantation and chronic cell transplantation can spare tissue, promote regeneration, and maximize the function of new axonal connections.

Clinical Translation

This strategy could open a new therapeutic window for SCI, particularly in cases of penetrating injury, where strategies that can enable true axonal regeneration may be required to open a path for recovery of function.

hNSC Integration

Multipotent hNSC that enter the PLG bridge exhibit the potential to integrate with host circuitry via differentiation into myelinating oligodendrocytes and synaptically connected neurons.

Study Limitations

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