Abstract
Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model. In situ preconditioning was induced by a combinatory treatment of BM-MSCs with genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) and heart-derived extracellular matrix (hdECM) hydrogel. Subsequently, our results demonstrated that in situ preconditioning with cell mixture substantially improved the survival/retention of BM-MSCs in the MI-induced rat hearts. Enhanced retention of BM-MSCs ultimately led to a significant cardiac function improvement, which was derived from the protection of myocardium and enhancement of vessel formation in the MI hearts. The results provide compelling evidence that in situ preconditioning devised to improve the therapeutic potential of BM-MSCs can be an effective strategy to achieve cardiac repair of MI hearts.
Highlights
Ischemic heart disease, such as myocardial infarction (MI), has long been the single largest leading cause of deaths and disabilities worldwide [1]
HGF-eMSCs secreted a substantial concentration of human basic fibroblast growth factor and HGF proteins compared with bone marrow-derived mesenchymal stem cells (BM-MSCs) determined by a cytokine array kit (Figure 1B)
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Summary
Ischemic heart disease, such as myocardial infarction (MI), has long been the single largest leading cause of deaths and disabilities worldwide [1]. Due to exceedingly minimal self-regenerative potential in the heart as well as limited therapeutic options, cell-based cardiac regeneration therapy has emerged as one of the most promising alternatives for treating damaged hearts [2]. Multiple clinical trials for assessing the possibility of using hMSCs as cellular agents for treating heart disease were conducted worldwide [7]. While some of these trials have demonstrated moderate improvement of left ventricular function, most clinical trials failed to report significant functional enhancement following the administration of hMSCs [8,9,10,11]
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