DNA Methylation Inhibitors, 5‐azacytidine and Zebularine Potentiate the Transdifferentiation of Rat Bone Marrow Mesenchymal Stem Cells into Cardiomyocytes. Issue 4 (18th July 2013)

• Record Type: Journal Article
• Authors: Naeem, Nadia; Haneef, Kanwal; Kabir, Nurul; Iqbal, Hana'a; Jamall, Siddiqua; Salim, Asmat
• Is Part Of: Cardiovascular therapeutics. Volume 31:Issue 4(2013:Aug.)
• Page Start: 201
• Page End: 209
• Publication Date: 2013-07-18
• Subjects: Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular system -- Diseases -- Chemotherapy -- Periodicals; Cardiovascular Agents -- Periodicals; Cardiovascular Diseases -- drug therapy -- Periodicals; Agents cardiovasculaires -- Périodiques; Appareil cardiovasculaire -- Maladies -- Chimiothérapie -- Périodiques; 616.1005
• DOI: 10.1111/j.1755-5922.2012.00320.x
• Languages: English
• ISSNs: 1755-5914

Abstract

<abstract abstract-type="main" id="cdr320-abs-0001"> <title>Summary</title> <sec id="cdr320-sec-0001" sec-type="section"> <title>Background</title> <p>Mesenchymal stem cells (MSCs) have immense self‐renewal capability. They can be differentiated into many cell types and therefore hold great potential in the field of regenerative medicine. MSCs 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.</p> </sec> <sec id="cdr320-sec-0002" sec-type="section"> <title>Aims</title> <p>To achieve a better therapeutic option for cardiovascular regeneration, this study was carried out using MSCs treated with two synthetic compounds, zebularine and 5‐azacytidine. It can be expected that treated MSCs prior to transplantation may increase the likelihood of successful regeneration of damaged myocardium.</p> </sec> <sec id="cdr320-sec-0003" sec-type="section"> <title>Methods</title> <p>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 MSCs were cocultured with cardiomyocytes to see the fusion capability of these cells.</p> </sec> <sec id="cdr320-sec-0004" sec-type="section"> <title>Results</title> <p>mRNA and protein expressions of GATA4, Nkx2.5, and cardiac troponin T were observed in the treated MSCs. Coculture studies of MSCs and cardiomyocytes have shown improved fusion with zebularine‐treated MSCs as compared to untreated and 5‐azacytidine‐treated MSCs.</p> </sec> <sec id="cdr320-sec-0005" sec-type="section"> <title>Conclusion</title> <p>The study is expected to put forth another valuable aspect of certain compounds, that is, induction of transdifferentiation of MSCs into cardiomyocytes. This would serve as a tool for modified cellular therapy and may increase the probability of better myocardial regeneration.</p> </sec> </abstract>