Efficacy of Deferoxamine Mesylate in Serum and Serum-Free Media: Adult Ventral Root Schwann Cell Survival Following Hydrogen Peroxide-Induced Cell Death.

Abstract

Schwann cell (SC) transplantation shows promise in treating spinal cord injury as a pro-regenerative agent to allow host endogenous neurons to bridge over the lesion. However, SC transplants face significant oxidative stress facilitated by ROS in the lesion, leading to poor survival. deferoxamine mesylate (DFO) is a neuroprotective agent shown to reduce H₂O₂-induced cell death in serum-containing conditions. Here we show that DFO is not necessary to induce neuroprotection under serum-free conditions by cell survival quantification and phenotypic analysis via immunohistochemistry, Hif1α and collagen IV quantification via whole cell corrected total cell fluorescence, and cell death transcript changes via RT-qPCR. Our results indicate survival of SC regardless of DFO pretreatment in serum-free conditions and an increased survival facilitated by DFO in serum-containing conditions. Furthermore, our results showed strong nuclear expression of Hif1α in serum-free conditions regardless of DFO pre-treatment and a nuclear expression of Hif1α in DFO-treated SCs in serum conditions. Transcriptomic analysis reveals upregulation of autophagy transcripts in SCs grown in serum-free media relative to SCs in serum conditions, with and without DFO and H₂O₂. Thus, indicating a pro-repair and regenerative state of the SCs in serum-free conditions. Overall, results indicate the protectiveness of CDM in enhancing SC survival against ROS-induced cell death in vitro.