Effects Of Bone Marrow Mesenchymal Stem Cells Transplantation In Postinfarcted Rat Myocardium On Transient Outward Potassium Kv4.2 Of Ventricular Cardiomyocytes

Backgrounds: Bone marrow mesenchymal stem cells (MSCs) are undifferentiated multipotent cell population with the potential to be self-renewed. A variety of experiments and clinical studies suggested that MSCs can improve cardiac pump function after acute myocardial infarction. Moreover, concern that intramyocardial transplantation of cells could cause potentially life-threatening ventricular arrhythmias has been repeatedly reported. Transient Outward Potassium Current(Ito) is the first repolarization current when action potential occurs, which includes fast Ito and slow I_to. The study demonstrated that I_to is a important factor of tow phase reentry. The study on rat without genes Kv1.4 and Kv4.2 indicated prolongation of action potential duration, even with early afterdepolarization.Objectives: To investigate the effects of bone marrow mesenchymal stem cells (MSCs) implantation in postinfarcted rat myocardium on transient outward potassium Kv4.2 of cardiomyocytes in left ventricle, to assess the electrophysiological and arrhythmogenic effects and provide efficacy and safety evidences for MSCs therapy in AMI.Methods: Male MSCs are cultured and expanded using density gradient centrifugation. Seven days after intracardiac injection into a male rat left anterior descending (LAD) ligation model, cell survival and engraftment were identified by GFP immunofluorescence. Two weeks after transplantation, ventricular arrhythmias (VAs)inducibility were assessed by echocardiography and programmed electrical stimulation(PES). Left ventricular morphology was evaluated through H&E. Transplanted cells were observed by fluorescent microscope. RT-PCR and Western blot were used to identify expression of I_to Kv4.2.Results: 1. MSCs were negative for haemopoietic markers CD₃₄,CD₁₄ and CD45 and positive for CD₂₉, CD₄₄, and CD₁₀₅. MSCs cultured in differentiation medium led to Oil red-O-positive or Alizarin Red positive. Part of 5-azacytidine treated MSCs expressed cardiac marker troponin T. 2. Fluorescent microscope showed that MSC-derived cells survived. The expression of Kv4.2 in the MI group and MI-CM group was significantly lower than that in the sham-operating group. Compared to MI-CM group and MI group, expression of Kv4.2 was significantly increased. MSCs injection led to significantly reduced inducibility of VAs.Conclusion: The MSCs transplantation significantly reduced inducibility of VAs. The MSCs transplantation treatment can elevate the expression of Kv4.2 of AMI rats, which may be related to decrease of arrhythmias after MSCs transplantation.