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Simultaneous Electrical and Mechanical Stimulation to Enhance Cells' Cardiomyogenic Potential
Published on: January 18, 2019
Association of electrostimulation with cell transplantation in ischemic heart disease
Abdel Shafy1, Thomas Lavergne, Christian Latremouille
1Laboratory of Biosurgical Research, Pompidou Hospital, University of Paris, Paris, France.
Insights
Combining cell therapy with cardiac resynchronization therapy improves heart function in a sheep model. This dynamic approach enhances ventricular function and cell integration in infarcted hearts.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Biomedical Engineering
Background:
- Cell therapy for heart failure has been passive, mainly reducing fibrosis and remodeling.
- Cardiac resynchronization therapy (CRT) corrects conduction disorders in heart failure.
- Combining cell therapy with CRT may create dynamic cellular support.
Purpose of the Study:
- To evaluate myogenic cell transplantation in an ischemic heart model.
- To assess the impact of associated cardiac resynchronization therapy on cell therapy efficacy.
Main Methods:
- Myocardial infarction was induced in 22 sheep.
- Autologous myoblasts were injected into infarcted areas with or without pacemaker implantation.
- Atrial synchronized biventricular pacing was performed; echocardiography assessed function.
Main Results:
- Cell therapy with CRT significantly improved ejection fraction and limited left ventricular dilatation.
- Viable cells differentiated into myotubes with enhanced slow myosin expression in the electrostimulated group.
- Combined therapy increased diastolic wall thickening in the infarcted zone.
Conclusions:
- Biventricular pacing promotes synchronous contraction of transplanted cells and host myocardium, enhancing ventricular function.
- Electrostimulation supports myoblast differentiation and organization for improved cardiac work.
- Simultaneous cardiac pacing and cell therapy may benefit heart failure patients with infarct scars.
Background:
Until now, cell therapy has constituted a passive therapeutic approach; the only effects seem to be related to the reduction of the myocardial fibrosis and the limitation of the adverse ventricular remodeling. Cardiac resynchronization therapy is indicated in patients with heart failure to correct conduction disorders associated with chronic systolic and diastolic dysfunction. The association of electrostimulation with cellular cardiomyoplasty could be a way to transform passive cell therapy into "dynamic cellular support." Electrostimulation of ventricles following skeletal myoblast implantation should induce the contraction of the transplanted cells and a higher expression of slow myosin, which is better adapted for chronic ventricular assistance. The purpose of this study is to evaluate myogenic cell transplantation in an ischemic heart model associated with cardiac resynchronization therapy.
Methods:
Twenty two sheep were included. All animals underwent myocardial infarction by ligation of 2 coronary artery branches (distal left anterior descending artery and D2). After 4 weeks, autologous cultured myoblasts were injected in the infarcted areas with or without pacemaker implantation. Atrial synchronized biventricular pacing was performed using epicardial electrodes. Echocardiography was performed at 4 weeks (baseline) and 12 weeks after infarction.
Results:
Echocardiography showed a significant improvement in ejection fraction and limitation of left ventricular dilatation in cell therapy with cardiac resynchronization therapy as compared with the other groups. Viable cells were identified in the infarcted areas. Differentiation of myoblasts into myotubes and enhanced expression of slow myosin heavy chain was observed in the electrostimulated group. Transplantation of cells with cardiac resynchronization therapy caused an increase in diastolic wall thickening in the infarcted zone relative to cells-only group and cardiac resynchronization therapy-only group.
Conclusions:
Biventricular pacing seems to induce synchronous contraction of transplanted myoblasts and the host myocardium, thus improving ventricular function. Electrostimulation was related with enhanced expression of slow myosin and the organization of myoblasts in myotubes, which are better adapted at performing cardiac work. Patients with heart failure presenting myocardial infarct scars and indication for cardiac resynchronization therapy might benefit from simultaneous cardiac pacing and cell therapy.
