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

Mahdi Ahmadi, Reza Rahbarghazi, Rana Keyhanmanesh, Fatemeh Mirershadi, Hossain Heiran, Hesam Saghaei Bagheri, Shirin Saberianpour, Aysa Rezabakhsh, Aref Delkhosh, Yasin Bagheri, Hadi Rajabi
2020 unpublished
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;
more » ... ized 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<0.05). Both c-kit+ 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<0.05). We also found that c-kit+ 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<0.05). c-kit- 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.
doi:10.21203/rs.3.rs-21216/v1 fatcat:4neswa7qxrhafckmlfkdcqveru