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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., (© 2022. The Author(s).)

(I-L) Effects of growth factors in inflammatory environment on TNF- (I), IL-6 (J), TGF- (K) and IL-10 (L) cytokine levels. Graph: Figure 5 Effects of PDGF and VEGF on the SC cytokine profile in inflammatory and non-inflammatory conditions (A-D) Effects of an inflammatory environment on SC-mediated secretion of pro-inflammatory cytokines TNF- (A), IL-6 (B) and anti-inflammatory cytokines TGF- (C), IL-10 (D). [Extracted from the article]