Department of Cardiology and Department of Molecular Cell Biology (MCB), Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Abstract
Injection of (stem) cells into the damaged heart has a positive effect on cardiac function. In this thesis two strategies for improving myocardial regeneration over classical cell therapy were investigated. The first is to induce cardiomyogenic differentiation by genetically engineering cells to express the transcription factor myocardin (a regulator of cardiomyocyte differentiation). We found that overexpression of myocardin induces a large part of the cardiac muscle gene expression program in various non-muscle cells. Forced expression of myocardin enables cardiac infarction scar fibroblasts to conduct a cardiac action potential, and injection of myocardin-transduced MSCs resulted in greater preservation of cardiac function and reduced detrimental remodeling compared to untreated MSCs in a mouse model of myocardial infarction. Indicating that overexpression of myocardin endows cells with several beneficial properties of cardiomyocytes. We hypothesized that myocardial regeneration might be enhanced by including novel cell types with supportive functions in cell therapy strategies. We found that the mesothelial cells of the human epicardium, like embryonic epicardium-derived cells (EPDCs) can form fibroblasts and smooth muscle cells. Indicating that EPDCs from human adults recapitulate at least part of the differentiation potential of their embryonic counterparts, which form various essential supportive cell types during heart development.UBL - phd migration 201
