Author/Authors :
Rahbarghazi ، Reza Department of Applied Cell Sciences - Stem Cell Research Center, Faculty of Advanced Medical Sciences - Tabriz University of Medical Sciences , Kihanmanesh ، Rana Tuberculosis and Lung Diseases Research Center - Tabriz University of Medical Sciences , Rezaie ، Jafar Solid Tumor Research Center, Research Institute for Cellular and Molecular Medicine - Urmia University of Medical Sciences , Mirershadi ، Fatemeh Department of Physiology - Islamic Azad University, Ardabil Branch , Heiran ، Hossain Department of Physiology - Faculty of Medicine - Tabriz University of Medical Sciences , Saghaei Bagheri ، Hesam Stem Cell Research Center - Tabriz University of Medical Sciences , Saberianpour ، Shirin Vascular and Endovascular Surgery Research Center - Mashhad University of Medical Science , Rezabakhsh ، Aysa Physical Medicine and Rehabilitation Research Center, Aging Research Institute - Tabriz University of Medical Sciences , Delkhosh ، Aref Stem Cell Research Center - Tabriz University of Medical Sciences , Bagheri ، Yasin Young Researchers and Elite Club - Islamic Azad university, Tabriz Branch , Rajabi ، Hadi Stem Cell Research Center - Tabriz University of Medical Sciences , Ahmadi ، Mahdi Tuberculosis and Lung Diseases Research Center, Stem Cell Research Center - Tabriz University of Medical Sciences
Abstract :
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 marrowderived ckit+ cells were enriched by MACS. Animals were classified into four groups (6 rats each). Control rats received PBS intratracheally; Ovalbuminsensitized rats received PBS intratracheally; Ovalbuminsensitized rats received PBS intratracheally containing 3×105 c-kit+ and ckit cells. Cells were stained with Dil fluorescent dye to track in vivo condition. Pathological changes were monitored in asthmatic rats after transplantation of ckit+ and ckit cells. Serum levels of IL4 and INFγ were measured by ELISA. Transcription of miRNAs (-126 and 133) was assessed by realtime PCR analysis.Results: Pathological examination and Th1 and Th2 associated cytokine fluctuation confirmed the occurrence of asthma in rats indicated by chronic changes and prominent inflammation compared with the control group (p 0.05). Both c-kit+ and ckit cells were verified in pulmonary niche. Administration of ckit positive cells had the potential to change INF-γ/IL4 ratio close to the normal values compared with matchedcontrol asthmatic rats (p 0.05). We also found that ckit+ cells regulated the expression of miRNA-126 and 133, indicated by an increase of miRNA-133 and decrease of miRNA-126 compared with cellfree sensitized groups (p 0.05). Conclusion: ckit cells were unable to promote any therapeutic outcomes in the asthmatic milieu. c-kit+ cells had the potential to diminish asthmarelated pathologies presumably by controlling the transcription of miRNA-126 and -133.
Keywords :
Cell therapy , Histological changes , Lung , Ovalbumin , Rat
