Title : 2-Deoxycytidine Differentiates Cord MSCs into cardiomyocytes in vitro and Improves Cardiac Function in vivo
Abstract:
Introduction: - Small molecules are wisely used to induce differentiation in stem cell. 2'-deoxycytidine (DC), belong to cytidine family is used as demethylating agent. It stimulates the cardiac specific genes and proteins expression and directs Mesenchymal Stem Cells differentiation towards cardiomyogenic lineage.
Aims: Our aim was to analyze 2'-deoxycytidine activated rat umbilical cord derived mesenchymal stem cells (UC-MSCs) for their potential role in adhesion and cardiac differentiation.
Methods: Myocardial infarction (MI) was produced in Wistar rats by occlusion of the left anterior descending coronary artery. MSCs were treated with 2'-deoxycytidine to activate cardiac specific genes. Normal (untreated) and DC-treated MSCs were transplanted through intramyocardial injection in respective groups. Cardiac function was assessed by echocardiography at 2 and 4 weeks after cell transplantation. Histological analysis was performed to observe changes at tissue level.
RESULTS:- Homing of DC-treated MSCs was significantly (***P<.001) higher as compared to normal MSCs in the infarcted hearts. This may be due to increase in the gene expression of some of the cell adhesion molecules as evident by qRT-PCR analysis. Significant (***P<.001) improvement in the restoration of heart function in terms of left ventricular diastolic and systolic internal diameters (LVIDd, LVIDs), % ejection fraction, % fraction shortening and end-systolic and end-diastolic volumes were observed in DC-treated MSCs as compared to the MI model. Histological analyses showed significant (***P<.001) reduction in scar formation in the DC-treated group. Differentiation of treated MSCs into functional cardiomyocytes was evident through immunohistochemical staining. LV wall thickness was also preserved significantly (***P<.001). Blood vessel formation was more pronounced in DC-treated group although both cell therapy groups showed significant increase as compared to MI model.
CONCLUSION:- Our findings showed that activation of cardiac specific genes through DC improves cardiac function through better survival, adhesion and differentiation of transplanted cells. Transplantation of these MSCs in the infarct area restored functional myocardium.
