The optimization of cell therapy by combinational application with apicidin-treated mesenchymal stem cells after myocardial infarction.
Although mesenchymal stem cells (MSC) have been shown to be safe in preclinical studies of cardiovascular disease, multiple meta-analyses have debated whether functional improvement is significant or not. The cardiac differentiation from MSC is achievable using cardiogenic factors, however, the high cost and long culture period may limit the applications. Here, we developed a novel method to optimize the therapeutic outcome for myocardial infarction (MI). Treatment of MSC with apicidin, a histone deacetylase inhibitor, dramatically increased the expressions of cardiac markers such as GATA4, Nkx2.5, and cardiac troponin I (cTnI). In AC/MSC, stemness-related genes and yes-associated protein (YAP), a potent oncogene that drives cell proliferation, were significantly suppressed. Furthermore apicidin treatment or YAP knockdown downregulated miR-130a expression followed by induction of cardiac markers in MSC. In the comparison study, we found that both cardiac gene induction and angiogenesis were most prominent in the mixture of non-treated MSC and AC/MSC (Mix). Using mouse MI model, we show that application of Mix was strongly associated with cardiac differentiation of injected MSC and improved cardiac performance. Our results suggest that suppression of YAP/miR-130a shifts MSC cell fate toward cardiac lineage and identify apicidin as a potential pharmacological target for therapeutic development.
['Cho|Dong Im|DI|', 'Kang|Wan Seok|WS|', 'Hong|Moon Hwa|MH|', 'Kang|Hye Jin|HJ|', 'Kim|Mi Ra|MR|', 'Kim|Min Chul|MC|', 'Kim|Yong Sook|YS|', 'Ahn|Youngkeun|Y|']
D000818:Animals D015415:Biomarkers D001706:Biopsy D018797:Cell Cycle Proteins D002454:Cell Differentiation D000066673:Cell Self Renewal D064987:Cell- and Tissue-Based Therapy D004195:Disease Models, Animal D015870:Gene Expression D000071679:Glycogen Synthase Kinase 3 beta D007150:Immunohistochemistry D000090062:Kruppel-Like Factor 4 D051741:Kruppel-Like Transcription Factors D008297:Male D045164:Mesenchymal Stem Cell Transplantation D059630:Mesenchymal Stem Cells D051379:Mice D035683:MicroRNAs D009203:Myocardial Infarction D018919:Neovascularization, Physiologic D010456:Peptides, Cyclic D051176:beta Catenin
mesenchymal stem cell myocardial infarction differentiation apicidin cotransplantation