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  4. In vitro modulation of Schwann cell behavior by VEGF and PDGF in an inflammatory environment

In vitro modulation of Schwann cell behavior by VEGF and PDGF in an inflammatory environment

Scientific Reports, 2022 · DOI: 10.1038/s41598-021-04222-7 · Published: January 13, 2022

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

This study explores how two growth factors, VEGF and PDGF, affect Schwann cells (SCs) in an inflammatory environment, relevant to spinal cord injury (SCI) treatment. SCs are important for nerve repair, and combining them with growth factors could enhance regenerative outcomes after SCI. The researchers found that inflammation reduces the ability of SCs to clear myelin debris, a key obstacle after SCI. However, adding VEGF and PDGF, particularly PDGF, improved the SCs' myelin-clearing ability even in the presence of inflammation. PDGF also reduced the production of a pro-inflammatory cytokine (TNF-α) by SCs, suggesting it can create a more favorable environment for nerve regeneration. These findings suggest that using VEGF and/or PDGF with SC transplantation could be beneficial for SCI therapy.

Study Duration
Not specified
Participants
Primary mouse SCs from S100β-DsRed transgenic mice
Evidence Level
In vitro study

Key Findings

  • 1
    Inflammation impairs SC-mediated clearance of myelin debris, but the addition of VEGF and PDGF (alone and combined) improved phagocytosis, with PDGF eliciting the strongest effect.
  • 2
    PDGF reduces secretion of the pro-inflammatory cytokine TNF-α by SCs in an inflammatory environment, while IL-6 and anti-inflammatory cytokines (TGF-β and IL-10) remain unaltered.
  • 3
    PDGF downregulates the expression of the myelination-associated gene Oct6 (Pou3f1) in the presence of an inflammatory environment, suggesting a shift towards nerve repair.

Research Summary

This in vitro study investigates the effects of VEGF and PDGF on Schwann cell (SC) behavior within an inflammatory environment, mimicking conditions after spinal cord injury (SCI). The aim is to determine if these growth factors can enhance SC-mediated myelin debris clearance, modulate cytokine expression, and promote nerve repair. The study reveals that inflammation impairs SC-mediated phagocytosis of myelin debris, but VEGF and PDGF, especially PDGF, can improve this process. PDGF also reduces the secretion of the pro-inflammatory cytokine TNF-α and downregulates the myelination-associated gene Oct6. Overall, the results suggest that combining VEGF and/or PDGF with SC transplantation could be a beneficial strategy for SCI therapy by promoting myelin clearance, reducing inflammation, and shifting SCs towards a nerve-repairing phenotype.

Practical Implications

SCI Therapy Enhancement

Combining VEGF and/or PDGF with SC transplantation may improve regenerative outcomes in SCI.

Targeted Myelin Clearance

PDGF can be used to enhance SC-mediated myelin phagocytosis in a pro-inflammatory environment.

Inflammation Modulation

PDGF can reduce the risk of further damage to the surrounding environment by suppressing pro-inflammatory cytokine TNF-α.

Study Limitations

  • 1
    In vitro study may not fully reflect in vivo conditions.
  • 2
    Heterogeneous cell population in assays may influence the results.
  • 3
    Efficacy of growth factors needs to be confirmed in vivo.

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