Deferoxamine promotes mesenchymal stem cell homing in noise‐induced injured cochlea through PI3K/AKT pathway |
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Authors: | AA Peyvandi H‐A Abbaszadeh N Ahmady Roozbahany A Pourbakht S Khoshsirat H Haddadzade Niri H Peyvandi S Niknazar |
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Institution: | 1. Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;3. G. Raymond Chang School, Ryerson University, Toronto, Canada;4. Department of Audiology, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran;5. Yale University, New Haven, CT, USA |
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Abstract: | 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. |
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Keywords: | CXCR4 deferoxamine
NIHL
PI3K/AKT pathway stem cell homing |
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