The optimization of cell therapy by combinational application with apicidin-treated mesenchymal stem cells after myocardial infarction

Oncotarget
Dong Im ChoYoungkeun Ahn

Abstract

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 sugge...Continue Reading

References

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Citations

Dec 12, 2017·Journal of Cellular Physiology·Tao ZhouSuining Li
Feb 6, 2018·Chonnam Medical Journal·Yong Sook Kim, Youngkeun Ahn
Jan 10, 2019·Stem Cells International·Zhi ChenWei Eric Wang
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Boon C HengXuliang Deng
Nov 7, 2018·Experimental & Molecular Medicine·Soo Yeon LimYoungkeun Ahn

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Methods Mentioned

BETA
genetic modification
flow cytometry
PCR
transfection
biopsy
Assay
electrophoresis

Software Mentioned

Pro
CellQuest Pro
Image Reader
Zeiss LSM
Image
Elements
NIS
Image J
CURE
SPSS

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