Abstract
Transplanted mesenchymal stem cells (MSCs) have been shown to contribute to myocardial repair after myocardial infarction (MI), primarily through production and secretion some growth factors and cytokines related to cell survival and regeneration. Further improvement of the therapeutic potential of MSCs appears to be an attractive strategy for MI treatment. CXC chemokine receptor (CXCR) 7 is the receptor for stromal cell-derived factor-1 (SDF-1), an important chemokine that is essential for tissue repair and angiogenesis. SDF-1/CXCR7 axis plays a critical role in the mobilization, recruitment and function of MSCs during tissue regeneration. Here, we depleted miR-142 that targets CXCR7 in MSCs cells through expression of antisense of miR-142, resulting in enhanced expression of CXCR7 in these miR-142-depleted MSCs (md-MSCs). In vitro, presence of md-MSCs reduced hypoxia-induced cardiac muscle cell apoptosis in a more pronounced manner than MSCs. In vivo, compared to transplantation of MSCs, transplantation of md-MSCs further enhanced cardiac re-vascularization and further improved cardiac functions after MI in mice. Together, our data suggest that depletion of miR-142 in MSCs may improve their therapeutic effects on MI.
Highlights
Myocardial infarction (MI) is a hallmark for all coronaryartery diseases (CAD), and effective prevention from the loss and effective enhancement of the regeneration of cardiomyocytes after myocardial infarction (MI) are critical for a successful therapy for CAD [1].Recent evidence has demonstrated the effectiveness of mesenchymal stem cells (MSCs)based therapy for MI [2,3,4,5]
Since CXCR7 is critical for the therapeutic effects of MSCs in treating different diseases including MI, we aimed to enhance its expression in MSCs through modulation of its protein translation via miRNA
We performed bioinformatics analyses to search for miRNAs that have Watson-Crick pairing to the 3′-untranslated region (3′-UTR) of CXCR7 mRNA
Summary
Myocardial infarction (MI) is a hallmark for all coronaryartery diseases (CAD), and effective prevention from the loss and effective enhancement of the regeneration of cardiomyocytes after MI are critical for a successful therapy for CAD [1]. Recent evidence has demonstrated the effectiveness of mesenchymal stem cells (MSCs)based therapy for MI [2,3,4,5]. Bone-marrow-derived mesenchymal stem cells (MSCs) are characterized by specific surface antigen expression for Sca-1, CD90 and CD105, and absent expression for CD34, CD45 and HLA-DR [6,7,8]. MSCs have multipotent differential potential, and could be induced to differentiate into cells of mesodermal origin, including adipocytes, osteocytes and chondrocytes [9]. MSCs have been applied to promote cardiac muscle repair and regeneration after MI. Further improvement of the therapeutic potential of MSCs appears to be an attractive strategy for MI treatment
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