Open AccessDeferoxamine promotes mesenchymal stem cell homing in noise‐induced injured cochlea through PI 3K/ AKT pathway
Author(s) -
Peyvandi A.A.,
Abbaszadeh H.A.,
Roozbahany N. Ahmady,
Pourbakht A.,
Khoshsirat S.,
Niri H. Haddadzade,
Peyvandi H.,
Niknazar S.
Publication year - 2018
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12434
Subject(s) - homing (biology) , protein kinase b , mesenchymal stem cell , stem cell , pi3k/akt/mtor pathway , cochlea , immunology , microbiology and biotechnology , biology , chemistry , medicine , signal transduction , anatomy , ecology
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 ( CXCR 4) expression. We examined whether DFO can enhance mesenchymal stem cells ( MSC s) homing in noise‐induced damaged cochlea by PI 3K/ 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 CXCR 4 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 + LY 294002 (The PI 3K inhibitor)‐treated MSC s. Following chronic exposure to 115 dB white noise, MSC s 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 CXCR 4 expression in MSC s compared to non‐treated cells. DFO pre‐conditioning significantly increased the homing ability of MSC s into injured ear compared to normal MSC s. These effects of DFO were blocked by LY 294002. Conclusions Pre‐conditioning of MSC s by DFO before transplantation can improve stem cell homing in the damaged cochlea through PI 3K/ AKT pathway activation.