Intravenous administration of bone marrow mesenchymal stromal cells is safe for the lung in a chronic myocardial infarction model

Abstract

Aims: Intravenous administration of bone marrow mesenchymal stromal cells (MSCs) is an attractive option for the treatment of myocardial infarction (MI). Previous studies revealed that MSC infusion could limit the deterioration of cardiac function following acute MI; however, little is known regarding the safety and efficacy of MSC infusion for chronic MI. In this study, we address cell retention after intravenous injection in a chronic MI model, and the fate and impact of distributed MSCs in the lung and heart. Methods: MI model was created by coronary ligation in female rats. A total of 3 weeks later, 5 × 106 bromodeoxyuridine-labeled male MSCs in 300 µl phosphate-buffered solution (PBS) were infused intravenously (cell transplantation group, n = 37). The same volume of PBS was infused and served as the control group (n = 37). A total of 20 healthy rats received intravenous PBS injections and served as the sham group. 1 day and 4 weeks after cell or PBS infusion, echocardiography was performed and cell retention was evaluated by quantitative real-time PCR. The fate of the migrated cells was detected through immunohistochemistry and the expression of inflammatory and anti-inflammatory protein was evaluated in lung and heart. The lung and heart function was also assessed. Results: 1 day after cell implantation, the percentage of retained cells relative to the initial number of injected cells in heart and lung was 0.54 ± 0.19% and 51.69 ± 12.96%, respectively. After 4 weeks, it decreased to 0.24 ± 0.09% and 0.22 ± 0.17%. The entrapped MSCs did not differentiate into alveolar epithelial-like cells. Likewise, the left ventricular function was not improved. No adverse effects on lung function were observed after cell infusion. The expression of pro-inflammatory factors, including TNF-α, IL-1β, malondialdehyde and myeloperoxidase, and anti-inflammatory factors, including TNF-α-induced protein 6, in the lung and heart was not significantly regulated after cell transplantation. Conclusion: Although the majority of intravenous infused cells were harbored in the lung, they did not cause deterioration of lung function. However, they did not activate the release of inflammatory/anti-inflammatory proteins, or stimulate angiogenesis or myogenesis in the old infarcted myocardium. Thus, intravenous administration of MSCs for chronic MI needs further experimental study.