Abstract
Stem cell-based therapies have the potential to dramatically transform the treatment and prognosis of myocardial infarction (MI), and mesenchymal stem cells (MSCs) have been suggested as a promising cell population to ameliorate the heart remodeling in post-MI. However, poor implantation and survival in ischemic myocardium restrict its efficacy and application. In this study, we sought to use the unique mode of action of Chinese medicine to improve this situation. Surrounding the myocardial infarct area, we performed a multi-point MSC transplantation and administered in conjunction with Danhong injection, which is mainly used for the treatment of MI. Our results showed that the MSC survival rate and cardiac function were improved significantly through the small animal imaging system and echocardiography, respectively. Moreover, histological analysis showed that MSC combined with DHI intervention significantly reduced myocardial infarct size in myocardial infarcted mice and significantly increased MSC resident. To investigate the mechanism of DHI promoting MSC survival and cell migration, PCR and WB experiments were performed. Our results showed that DHI could promote the expression of CXC chemokine receptor 4 in MSC and enhance the expression of stromal cell–derived factor-1 in myocardium, and this effect can be inhibited by AMD3100 (an SDF1/CXCR4 antagonist). Additionally, MSC in combination with DHI interfered with MI in mice and this signifies that when combined, the duo could the expression of vascular endothelial growth factor (VEGF) in the marginal zone of infarction compared with when either MSC or DHI are used individually. Based on these results, we conclude that DHI enhances the residence of MSCs in cardiac tissue by modulating the SDF1/CXCR4 signaling pathway. These findings have important therapeutic implications for Chinese medicine-assisted cell-based therapy strategies.
Highlights
Cardiovascular disease, including atherosclerosis, stroke, and myocardial infarction (MI), is the leading cause of death in the world (Clark, 2013)
The ejection fraction (EF), fractional shortening (FS), E/A, and early and late diastolic phase (E /A) of mice in mesenchymal stem cells (MSC) only, danhong injection (DHI) only, and MSC plus DHI group were improved in different degrees in 2 and 4 weeks after MI (p < 0.05 or p < 0.01), except for E/A in group B mice (Figure 2); compared with MSCs only or DHI only mice, the EF and FS were significantly increased in MSC plus DHI group mice in 2 weeks after MI (Figures 2A,B)
These data indicated that DHI promoted the role of MSC in improving cardiac function, which usually gets weaker over time in MI mice
Summary
Cardiovascular disease, including atherosclerosis, stroke, and MI, is the leading cause of death in the world (Clark, 2013). Despite the significant progress in treatment, the prognosis of patients with MI or HF is still poor, and the current therapeutic approaches are palliative, because they do not solve the potential problems leading to loss of heart tissues (Sanganalmath and Bolli, 2013). A therapy being developed to eliminate the underlying cause of HF, not just to achieve damage control, is considered to be an effective treatment for the recovery of cardiac function currently. It is limited by insufficient donor organs and the requirement for lifelong immunosuppression (Stehlik et al, 2011; Sanganalmath and Bolli, 2013; Huang et al, 2016). It is necessary to make efforts to develop new therapies that could repair and regenerate the myocardium
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