Adoptive transfer of T cell immunity has been proposed as an attractive form of cancer immunotherapy in cases where the endogenous T cell repertoire is immune tolerant. In this thesis murine models... Show moreAdoptive transfer of T cell immunity has been proposed as an attractive form of cancer immunotherapy in cases where the endogenous T cell repertoire is immune tolerant. In this thesis murine models are used to study two different approaches to generate T cell grafts with defined tumor specificities. First the feasibility of minor antigen specific T cell depletion to limit the development of Graft-versus-Host Disease after allogeneic stem cell transplantation in combination with donor lymphocyte infusions is addressed. In the second part T cell receptor gene transfer is used to generate tumor specific T cells. Show less
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... Show moreInjection 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. Show less
