Cardiogenic Differentiation of Murine Bone Marrow-Derived Mesenchymal Stem Cells by 5-Azacytidine: A Follow-up In vitro Study.

Abstract

Background:Cell-based therapy is a promising tool in the management of myocardial infarction.Aim of the Work:The aim of this study is to examine the in vitro potential differentiation of murine bone marrow (BM)-derived stem cells into cardiomyocytes using 5-azacytidine after 1, 3, and 5 weeks and follow it up after 8 weeks.Materials and Methods:BM-derived mesenchymal stem cells (MSCs) were extracted from the bones of adult albino rats. MSCs were induced with 10 μM 5-azacytidine for 24 h. The cells were examined after 1, 3, 5, and 8 weeks. Cell characterization with immunocytochemistry for detection of CD105, desmin, and T-troponin and transmission electron microscopy was performed.Results:The 5-azacytidine-induced MSCs showed light and electron microscopic histological characteristics resembling cardiomyocytes and progressively expressed the cardiac muscle-specific markers over the 1st, 3rd, and 5th weeks, yet by the 8th week, these parameters were significantly downregulated.Conclusion:Prolonged survival of 5-azacytidine-induced MSCs in culture beyond the 8th week resulted in loss of the newly acquired cardiomyocyte characteristics. It is not recommended to prolong the maintenance of 5-azacytidine-induced MSCs in culture on the hope of increasing its cardiogenic potentiality beyond 5 weeks.