Intratracheal administration of bone marrow c-kit+ cells offered hopes in ameliorating asthmatic pathologies via the control of miRNA-133 and -126

Background There are still challenges regarding c-kit+ cells therapeutic outcome in the clinical setting. Here, we examined of c-kit+ cells effect on the alleviation of asthma by modulating miRNAs expression.MethodsTo induce asthma, male rats were exposed to ovalbumin. Bone marrow-derived c-kit+ cells were enriched by MACS. Animals were classified into four groups (each in 6 rats). Control rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally containing 3×105 c-kit+ and c-kit- cells. Cells were stained with Dil fluorescent dye to track in vivo condition. Pathological changes were monitored in asthmatic rats after transplantation of c-kit+ and c-kit- cells. Serum levels of IL-4 and INF-γ were measured by ELISA. Transcription of miRNAs (-126 and 133) were assessed by real-time PCR analysis.ResultsPathological examination, Th1 and Th2 associated cytokines fluctuation confirmed the occurrence of asthma in rats indicated by chronic changes and prominent inflammation compared to the control group (p+ and c-kit- cells were verified in pulmonary niche. Administration of c-kit positive cells had potential to changes INF-γ/IL-4 ratio and closed to the normal values compared to matched-control asthmatic rats (p+ cells regulated the expression of miRNA-126 and -133, indicated by increase of miRNA-133 and decrease of miRNA-126 compared to cell-free sensitized groups (p- cells were unable to promote any therapeutic outcomes in asthmatic milieu.ConclusionsIn overall, c-kit+ cells had potential to diminish asthma-related pathologies presumably by controlling the transcription of miRNA-126 and -133.