Attenuation Of Cigarette Smoke-Induced Cardiac Dysfunction And Inflammation By Mesenchymal Stem Cells In Rat

Abstract

Rationale: Cigarette smoke (CS) is recognized as a major cause of cardiovascular disease (CVD), particularly in those with chronic obstructive pulmonary disease (COPD). Oxidative stress and inflammatory responses may play an important role in the pathophysiological processes of CS-induced cardiac damage. Stem cell therapy has the potential to be a promising treatment in the field of regenerative cardiovascular medicine. Mesenchymal stem cells (MSC), was regarded as a leading candidate for cell-based therapy for myocardial infarction. The aim of this study is to investigate the effect of bone marrow-derived MSCs (BM-MSC) and induced pluripotent stem cell-derived MSC (IPSC-MSC) on cardiac function and inflammation in the cigarette smoke-exposed rat model. Methods: Male Sprague-Dawley rats (aged 6-7 weeks) were randomly divided into sham air (SA) group, cigarette smoke (CS) group, IPSC-MSC treatment (IP/CS) group and BM-MSC treatment (BM/CS) group respectively. All the animals were exposed to 4% CS except SA group to fresh air for 1h each day for 56 days in the ventilated chambers. IPSC-MSCs or BM-MSCs (3×10 cells) were injected intravenously 6 via tail vein in IP/CS or BM/CS group on day 29 and day 43. Animals were anaesthetized 24 hours after the last exposure for cardiac function examination by echocardiography. Cardiac levels of inflammatory and anti-inflammatory markers were measured by ELISA. Results: From echocardiograph, IPSC-MSC had a better trend of reversing the CS-induced reduction in cardiac function by elevating left ventricular ejection fraction (LVEF) and fractional shortening (FS) than BM-MSC. Both IPSC-MSC and BM-MSC administrations were able to attenuate the CS-induced elevation of cardiac proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and cytokine-induced neutrophil chemoattractant-1 (CINC-1, resemble to human IL-8). IPSC-MSC also significantly restored CS-induced reduction of cardiac interleukin-10 (IL-10) and adiponectin, while BM-MSC had no such effect. Conclusion: Our findings found that IPSC-MSC treatment could alleviate the CS-induced cardiac dysfunction and attenuate cardiac inflammatory changes by inhibiting proinflammatory cytokines and restoring anti-inflammatory mediators in the CS-exposed rat model, suggesting the cardio-protective effects of IPSC-MSC therapy. This abstract is funded by: Hong Kong RGC_GRF 2010-2011 (HKU 774410M)