c-kit+ cells offer hopes in ameliorating asthmatic pathologies via regulation of miRNA-۱۳۳ and -۱۲۶

Objective(s): There are still challenges regarding c-kit+ cells’ therapeutic outcome in the clinical setting. Here, we examined the c-kit+ cell effect on the alleviation of asthma by modulating miRNAs expression.Materials and Methods: To induce asthma, male rats were exposed to ovalbumin. Bone marrow-derived c-kit+ cells were enriched by MACS. Animals were classified into four groups (۶ rats each). Control rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally containing ۳×۱۰۵ 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-۴ and INF-γ were measured by ELISA. Transcription of miRNAs (-۱۲۶ and ۱۳۳) was assessed by real-time PCR analysis.Results: Pathological examination and Th۱ and Th۲ associated cytokine fluctuation confirmed the occurrence of asthma in rats indicated by chronic changes and prominent inflammation compared with the control group (p <۰.۰۵). Both c-kit+ and c-kit- cells were verified in pulmonary niche. Administration of c-kit positive cells had the potential to change INF-γ/IL-۴ ratio close to the normal values compared with matched-control asthmatic rats (p <۰.۰۵). We also found that c-kit+ cells regulated the expression of miRNA-۱۲۶ and -۱۳۳, indicated by an increase of miRNA-۱۳۳ and decrease of miRNA-۱۲۶ compared with cell-free sensitized groups (p <۰.۰۵). Conclusion: c-kit- cells were unable to promote any therapeutic outcomes in the asthmatic milieu. c-kit+ cells had the potential to diminish asthma-related pathologies presumably by controlling the transcription of miRNA-۱۲۶ and -۱۳۳.

کلیدواژه ها:

Cell therapy ، Histological changes ، Lung ، Ovalbumin ، Rat