Open AccessDNA Methylation Inhibitors, 5‐azacytidine and Zebularine Potentiate the Transdifferentiation of Rat Bone Marrow Mesenchymal Stem Cells into Cardiomyocytes
Author(s) -
Naeem Nadia,
Haneef Kanwal,
Kabir Nurul,
Iqbal Hana'a,
Jamall Siddiqua,
Salim Asmat
Publication year - 2013
Publication title -
cardiovascular therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 46
eISSN - 1755-5922
pISSN - 1755-5914
DOI - 10.1111/j.1755-5922.2012.00320.x
Subject(s) - mesenchymal stem cell , transdifferentiation , medicine , dna methylation , cancer research , demethylating agent , dna demethylation , bone marrow , regeneration (biology) , azacitidine , stem cell , transplantation , regenerative medicine , cell therapy , microbiology and biotechnology , immunology , pathology , biology , gene expression , gene , biochemistry
Summary Background Mesenchymal stem cells ( MSC s) have immense self‐renewal capability. They can be differentiated into many cell types and therefore hold great potential in the field of regenerative medicine. MSC s can be converted into beating cardiomyocytes by treating them with DNA ‐demethylating agents. Some of these compounds are nucleoside analogs that are widely used for studying the role of DNA methylation in biological processes as well as for the clinical treatment of leukemia and other carcinomas. Aims To achieve a better therapeutic option for cardiovascular regeneration, this study was carried out using MSC s treated with two synthetic compounds, zebularine and 5‐azacytidine. It can be expected that treated MSC s prior to transplantation may increase the likelihood of successful regeneration of damaged myocardium. Methods The optimized concentrations of these compounds were added separately into the culture medium and the treated cells were analyzed for the expression of cardiac‐specific genes by RT ‐ PCR and cardiac‐specific proteins by immunocytochemistry and flow cytometry. Treated MSC s were cocultured with cardiomyocytes to see the fusion capability of these cells. Results mRNA and protein expressions of GATA 4, Nkx 2.5, and cardiac troponin T were observed in the treated MSC s. Coculture studies of MSC s and cardiomyocytes have shown improved fusion with zebularine‐treated MSC s as compared to untreated and 5‐azacytidine‐treated MSC s. Conclusion The study is expected to put forth another valuable aspect of certain compounds, that is, induction of transdifferentiation of MSC s into cardiomyocytes. This would serve as a tool for modified cellular therapy and may increase the probability of better myocardial regeneration.