Reza Rahbarghazi1, Rana Keyhanmanesh2, Mohammad Reza Aslani3, Mehdi Hassanpour4, Mahdi Ahmadi5. 1. 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. 2. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Ardabil Imam Khomeini Educational and Clinical Hospital, Ardabil University of Medical Sciences, Ardabil, Iran. Electronic address: mr.aslani@arums.ac.ir. 4. Stem Cell And Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran. 5. Tuberculosis and Lung Diseases 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. Electronic address: mahmadi@tbzmed.ac.ir.
Abstract
OBJECTIVES: Although excitements related to stem cell therapeutic outcomes have been highlighted enormously in asthma, the vast majority of works were conducted by researchers in animal models. Elucidating the mechanisms underlying the therapeutic effects of MSCs in asthmatic rats will provide a rational basis for assuring maximal safety of future clinical application of stem cells. In the current study, we sought to investigate the possible paracrine mechanism by which direct injection of MSCs and/or CM attenuate efficiently Th2-mediated inflammation in asthmatic lung tissues with the focus on ICAM-1 and VCAM-1 expression. METHODS: Male rats were divided into four experimental groups (n = 6); healthy rats received PBS intratracheally (group C), sensitized rats received PBS intratracheally (group S), sensitized rats received CM intratracheally (group S + CM), and sensitized rats received PBS intratracheally containing 2 × 106 rBMMSCs (group S + MSCs). Two weeks post-transplantation, the expression of interleukin (IL)-5, -12 and INF-γ, ICAM-1 and VCAM-1 were assessed along with pathological injuries and the homing of MSCs into the lung tissues. RESULTS: Our results showed CM, and notably rBMMSCs, returned the expression of IL-5, IL-12, INF-γ, ICAM-1, and VCAM-1 (p < 0.001 to p < 0.05) to the normal levels. Based on data, pathological injuries in pulmonary specimens of asthmatic rats were significantly attenuated (p < 0.001 to p < 0.05). Moreover, rBMMSCs had potential to successfully home to an asthmatic niche in cell-administrated rats. CONCLUSIONS: Our data noted the potency of CM and especially MSCs in ameliorating pathological changes via intra-tracheal route presumably by targeting ICAM-1 and VCAM-1 in lung tissues in rat asthma model.
OBJECTIVES: Although excitements related to stem cell therapeutic outcomes have been highlighted enormously in asthma, the vast majority of works were conducted by researchers in animal models. Elucidating the mechanisms underlying the therapeutic effects of MSCs in asthmatic rats will provide a rational basis for assuring maximal safety of future clinical application of stem cells. In the current study, we sought to investigate the possible paracrine mechanism by which direct injection of MSCs and/or CM attenuate efficiently Th2-mediated inflammation in asthmatic lung tissues with the focus on ICAM-1 and VCAM-1 expression. METHODS: Male rats were divided into four experimental groups (n = 6); healthy rats received PBS intratracheally (group C), sensitized rats received PBS intratracheally (group S), sensitized rats received CM intratracheally (group S + CM), and sensitized rats received PBS intratracheally containing 2 × 106 rBMMSCs (group S + MSCs). Two weeks post-transplantation, the expression of interleukin (IL)-5, -12 and INF-γ, ICAM-1 and VCAM-1 were assessed along with pathological injuries and the homing of MSCs into the lung tissues. RESULTS: Our results showed CM, and notably rBMMSCs, returned the expression of IL-5, IL-12, INF-γ, ICAM-1, and VCAM-1 (p < 0.001 to p < 0.05) to the normal levels. Based on data, pathological injuries in pulmonary specimens of asthmatic rats were significantly attenuated (p < 0.001 to p < 0.05). Moreover, rBMMSCs had potential to successfully home to an asthmatic niche in cell-administrated rats. CONCLUSIONS: Our data noted the potency of CM and especially MSCs in ameliorating pathological changes via intra-tracheal route presumably by targeting ICAM-1 and VCAM-1 in lung tissues in rat asthma model.