Deferoxamine promotes mesenchymal stem cell homing in noise-induced injured cochlea through PI3K/AKT pathway

Cell Prolif. 2018 Apr;51(2):e12434. doi: 10.1111/cpr.12434. Epub 2018 Jan 17.


Objective: Over 5% of the world's population suffers from disabling hearing loss. Stem cell homing in target tissue is an important aspect of cell-based therapy, which its augmentation increases cell therapy efficiency. Deferoxamine (DFO) can induce the Akt activation, and phosphorylation status of AKT (p-AKT) upregulates CXC chemokine receptor-4 (CXCR4) expression. We examined whether DFO can enhance mesenchymal stem cells (MSCs) homing in noise-induced damaged cochlea by PI3K/AKT dependent mechanism.

Materials and methods: Mesenchymal stem cells were treated with DFO. AKT, p-AKT protein and hypoxia inducible factor 1- α (HIF-1α) and CXCR4 gene and protein expression was evaluated by RT- PCR and Western blot analysis. For in vivo assay, rats were assigned to control, sham, noise exposure groups without any treatment or receiving normal, DFO-treated and DFO +LY294002 (The PI3K inhibitor)-treated MSCs. Following chronic exposure to 115 dB white noise, MSCs were injected into the rat cochlea through the round window. Number of Hoechst- labelled cells was determined in the endolymph after 24 hours.

Results: Deferoxamine increased P-AKT, HIF-1α and CXCR4 expression in MSCs compared to non-treated cells. DFO pre-conditioning significantly increased the homing ability of MSCs into injured ear compared to normal MSCs. These effects of DFO were blocked by LY294002.

Conclusions: Pre-conditioning of MSCs by DFO before transplantation can improve stem cell homing in the damaged cochlea through PI3K/AKT pathway activation.

Keywords: NIHL; CXCR4; PI3K/AKT pathway; deferoxamine; stem cell homing.

MeSH terms

  • Animals
  • Cochlea* / injuries
  • Cochlea* / metabolism
  • Cochlea* / pathology
  • Deferoxamine / pharmacology*
  • Gene Expression Regulation / drug effects
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Noise / adverse effects*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / biosynthesis*
  • Rats
  • Rats, Wistar
  • Receptors, CXCR4 / metabolism
  • Signal Transduction / drug effects*


  • Cxcr4 protein, rat
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Receptors, CXCR4
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Deferoxamine