期刊
CELL PROLIFERATION
卷 51, 期 2, 页码 -出版社
WILEY
DOI: 10.1111/cpr.12434
关键词
CXCR4; deferoxamine; NIHL; PI3K; AKT pathway; stem cell homing
类别
资金
- Hearing Disorders Research Center of Shahid Beheshti University of Medical Sciences, Tehran, Iran
ObjectiveOver 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 MethodsMesenchymal stem cells were treated with DFO. AKT, p-AKT protein and hypoxia inducible factor 1- (HIF-1) 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 24hours. ResultsDeferoxamine increased P-AKT, HIF-1 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. ConclusionsPre-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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