Journal of Stem Cell Research & Therapy

Epigenetic reprogramming of human cardiac mesenchymal stromal cells

3^rd International Conference and Exhibition on Cell & Gene Therapy

October 27-29, 2014 Embassy Suites Las Vegas, USA

Matteo Luca Vecellio

Accepted Abstracts: J Stem Cell Res Ther

Abstract:

Adult human cardiac mesenchymal-like stromal cells (CMSC) represent a relatively accessible cell type useful for therapy and their conversion into cardiovascular precursors represents a potential successful strategy for cardiac repair. We have recently reprogrammed CMSC into functionally competent cardiovascular precursors using epigenetically active small molecules. In particular CMSC were exposed to low serum (5% FBS) in presence of 5 μM all-trans Retinoic Acid (ATRA), 5 μM Phenyl Butyrate (PB), and 200 μM diethylenetriamine/nitric oxide (DETA/NO), a novel epigenetically active cocktail (EpiC). Upon treatment the expression of several cardiac stem cells and cardiovascular markers such as c-Kit, MDR-1, KDR, Nkx2.5, HCN4, NaV1.5, and α-MHC were up-regulated. In addition, profiling analysis revealed that a significant number of microRNAs (e.g. miR-133a, -210 and -34a) involved in cardiomyocyte biology and cell differentiation/proliferation was upregulated. Interestingly, 45% of EpiC-treated cells exhibited a TTX-sensitive sodium current and 20% of cells the pacemaker I(f) current. Mechanistically, the exposure to EpiC treatment introduced global histone modifications, characterized by increased levels of H3K4Me3 and H4K16Ac, as well as reduced H4K20Me3 and H3s10P, a pattern well-matched with reduced proliferation and chromatin relaxation. In addition, we just published that CMSC obtained from diabetic patients (D-CMSC) failed to differentiate in response to EpiC and other differentiation stimuli, highlighting a global histone code profiling with decreased acetylation (H3K9Ac; H3K14Ac), significantly increased histone methylation (H3K9Me3; H3K27Me3), downregulation of the GCN5-Related N-acetyltransferases (GNAT) p300/CBP associated factor (PCAF) and reduction in total HAT activity. Moreover DNA CpG island hypermethylation was detected at promoters of genes involved in cell growth control and genomic stability.

Biography :

Matteo Luca Vecellio has completed his PhD in Translational and Molecular Medicine in January 2012 at the University of Milan ? Bicocca. From June 2012 to June 2013, he started his Postdoctoral studies at Goethe University in Frankfurt am Main (Germany). He?s now Post Doc Scientist at the University of Oxford at the Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences.