Mahdi Ahmadi1, Reza Rahbarghazi2, Mohammad Reza Aslani1, Amir-Ali Shahbazfar3, Masoumeh Kazemi4, Rana Keyhanmanesh5. 1. Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Department of pathology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran. 4. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 5. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: rKeyhanmanesh@gmail.com.
Abstract
BACKGROUND: The major feature of asthma is governed by chronic airway inflammation. This investigation was proposed to achieve the suitable candidate for ameliorating long-term chronic asthmatic changes of respiratory tract. METHODS: 36 rats were classified into healthy (C) and ovalbumin (OVA)-sensitized animals (S). To sensitize, the rats were exposed to OVA over a course of 32±1days. One day after sensitization, equal six different groups were subjected to experimental procedure (n=6); Rats only received intratracheally 50ml PBS (CPT and SPT groups), 50μl conditioned medium (CM) (CST and SST groups) and 50μl PBS containing 2×106 rat bone marrow-derived mesenchymal stem cells (rBMMSCs) (CCT and SCT groups). Two weeks after treatment, tracheal responsiveness, immunologic responses and recruitment of rBMMSCs into the lung as well as pathological changes were evaluated. RESULTS: A high degree of tracheal responsiveness, total white blood cell and percentages of eosinophil and neutrophil was significantly recorded in all sensitized groups rather than of controls (p<0.001 to p<0.05). Of interest, all above-mentioned parameters decreased significantly in SST and notably SCT groups as compared to S group (p<0.001 to p<0.05). The results revealed decrease number of blood CD3+CD4+ and concurrent increase in CD3+CD8+ in all sensitized rats as compared to control (p<0.001 to p<0.05). Noticeably, no significant modulatory effects of either cell or CM administration were achieved on the CD3+CD4+ and CD3+CD8+ populations in non-asthmatic rats. Moreover, the number of CD3+CD4+ in SST and SCT groups tended to increase, which coincided with a decreased manner of CD3+CD8+ populations as compared with S group (p<0.001 to p<0.05). However, the CD3+CD4+ cells in SCT rats were significantly higher than the group SST (p<0.01) whereas CD3+CD8+ cells diminished simultaneously (p<0.001). Real-time PCR analysis further showed that both CM and particularly MSCs changed the expression of interleukin (IL)-4 and IL-10 in the asthmatic groups to the near level of control rats (p<0.001 to p<0.05). Histopathological analysis revealed a profound reduction of lungs injuries in asthmatic rats when received CM and peculiarly mesenchymal stem cells (p<0.01 to p<0.05). CONCLUSION: Our study shed light on the superior effects of rBMMSCs, rather than CM, in attenuating of chronic asthmatic changes in the rat model.
BACKGROUND: The major feature of asthma is governed by chronic airway inflammation. This investigation was proposed to achieve the suitable candidate for ameliorating long-term chronic asthmatic changes of respiratory tract. METHODS: 36 rats were classified into healthy (C) and ovalbumin (OVA)-sensitized animals (S). To sensitize, the rats were exposed to OVA over a course of 32±1days. One day after sensitization, equal six different groups were subjected to experimental procedure (n=6); Rats only received intratracheally 50ml PBS (CPT and SPT groups), 50μl conditioned medium (CM) (CST and SST groups) and 50μl PBS containing 2×106 rat bone marrow-derived mesenchymal stem cells (rBMMSCs) (CCT and SCT groups). Two weeks after treatment, tracheal responsiveness, immunologic responses and recruitment of rBMMSCs into the lung as well as pathological changes were evaluated. RESULTS: A high degree of tracheal responsiveness, total white blood cell and percentages of eosinophil and neutrophil was significantly recorded in all sensitized groups rather than of controls (p<0.001 to p<0.05). Of interest, all above-mentioned parameters decreased significantly in SST and notably SCT groups as compared to S group (p<0.001 to p<0.05). The results revealed decrease number of blood CD3+CD4+ and concurrent increase in CD3+CD8+ in all sensitized rats as compared to control (p<0.001 to p<0.05). Noticeably, no significant modulatory effects of either cell or CM administration were achieved on the CD3+CD4+ and CD3+CD8+ populations in non-asthmatic rats. Moreover, the number of CD3+CD4+ in SST and SCT groups tended to increase, which coincided with a decreased manner of CD3+CD8+ populations as compared with S group (p<0.001 to p<0.05). However, the CD3+CD4+ cells in SCT rats were significantly higher than the group SST (p<0.01) whereas CD3+CD8+ cells diminished simultaneously (p<0.001). Real-time PCR analysis further showed that both CM and particularly MSCs changed the expression of interleukin (IL)-4 and IL-10 in the asthmatic groups to the near level of control rats (p<0.001 to p<0.05). Histopathological analysis revealed a profound reduction of lungs injuries in asthmatic rats when received CM and peculiarly mesenchymal stem cells (p<0.01 to p<0.05). CONCLUSION: Our study shed light on the superior effects of rBMMSCs, rather than CM, in attenuating of chronic asthmatic changes in the rat model.
Authors: Jason M Aliotta; Mandy Pereira; Sicheng Wen; Mark S Dooner; Michael Del Tatto; Elaine Papa; Yan Cheng; Laura Goldberg; Corey E Ventetuolo; Olin Liang; James R Klinger; Peter J Quesenberry Journal: Stem Cells Transl Med Date: 2017-05-05 Impact factor: 6.940