Abstract
Background: The efficacy of transplantation of default mesenchymal stem cells (MSCs) is controversial because of their limited plasticity and decreased function in elderly patients with myocardial infarction (MI). We investigated whether epigenetically reprogrammed-MSCs ameliorate myocardial remodeling in a mouse model of MI. Methods: Bone marrow-derived MSCs were sequentially treated with 5 mM/L of valproic acid and 100 nM/L of 5-azacytidine for 48 hours. Quantitative RT-PCR was performed to evaluate the effect of epigenetic modifiers on the gene expression of MSCs. 2 x 105 default MSCs, 2 x 105 epigenetically reprogrammed-MSCs, or phosphate-buffered saline were injected into peri-infarct zone immediately after ligating proximal portion of left anterior descending artery. On days 28 after MI, in vivo cardiac magnetic resonance (CMR) and harvest of heart tissue was sequentially performed. Results: Epigenetic modification of MSCs induced gene expression of anti-inflammatory markers such as transforming growth factor-β, indoleamine 2,3-dioxygenase. Fibroblast growth factor-β increased 37.5% and myocyte-specific enhancer factor 2C increased 36.8% at the mRNA level. Transplantation of modified-MSCs showed improved ejection fraction on CMR. In histopathologic analysis, infarct size was significantly decreased in modified-MSCs transplanted mice (p=0.002). When assessing capillary density of peri-infarct zone, larger number of CD31+ staining vascular structures was observed in modified-MSCs transplanted mice. Immunofluorescence stain showed marked increase of CD4+CD25+Foxp3+ regulatory T cells as well as CD68+MR+ M2 macrophage and decrease of CD68+iNOs+ M1 macrophage in modified-MSCs transplanted mice. Conclusions: Transplantation of epigenetically reprogrammed-MSCs significantly improves cardiac function by modulating post-infarct inflammation and neoangiogenesis in a preclinical model of AMI.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
