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

Sci Rep. 2022 Jan 13;12(1):662. doi: 10.1038/s41598-021-04222-7.

Abstract

Peripheral glial cell transplantation with Schwann cells (SCs) is a promising approach for treating spinal cord injury (SCI). However, improvements are needed and one avenue to enhance regenerative functional outcomes is to combine growth factors with cell transplantation. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) are neuroprotective, and a combination of these factors has improved outcomes in rat SCI models. Thus, transplantation of SCs combined with VEGF and PDGF may further improve regenerative outcomes. First, however, we must understand how the two factors modulate SCs. In this in vitro study, we show that an inflammatory environment decreased the rate of SC-mediated phagocytosis of myelin debris but the addition of VEGF and PDGF (alone and combined) improved phagocytosis. Cytokine expression by SCs in the inflammatory environment revealed that addition of PDGF led to significantly lower level of pro-inflammatory cytokine, TNF-α, but IL-6 and anti-inflammatory cytokines (TGF-β and IL-10), remained unaltered. Further, PDGF was able to decrease the expression of myelination associated gene Oct6 in the presence of inflammatory environment. Overall, these results suggest that the use of VEGF and/or PDGF combined with SC transplantation may be beneficial in SCI therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Gene Expression / drug effects
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Inflammation Mediators / metabolism
  • Myelin Sheath / metabolism
  • Nerve Regeneration / genetics
  • Neuroprotective Agents
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism
  • Phagocytosis / drug effects
  • Phagocytosis / physiology
  • Platelet-Derived Growth Factor / pharmacology*
  • Rats
  • Schwann Cells / drug effects*
  • Schwann Cells / physiology*
  • Schwann Cells / transplantation
  • Spinal Cord Injuries / therapy
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • Inflammation Mediators
  • Neuroprotective Agents
  • Organic Cation Transport Proteins
  • Platelet-Derived Growth Factor
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A