Since the adult heart has minimal capacity to repair itself, myocardial infarction often leads to pathological remodeling and ultimately to the development of fatal heart failure. Upon ischemic... Show moreSince the adult heart has minimal capacity to repair itself, myocardial infarction often leads to pathological remodeling and ultimately to the development of fatal heart failure. Upon ischemic injury, the epicardium, the outer layer of the heart which is essential for cardiac development, becomes re-activated and displays reparative potential. In this process, epicardial epithelial-to-mesenchymal transition (epiMT) is an essential step. We hypothesize that the reparative capacity of the heart can be improved by enhancing the participation of the epicardium to cardiac repair, particularly by stimulating the occurrence of epiMT. Therefore, the aim of my thesis is to find ways to boost epiMT in the injured heart. In this thesis, we describe a cell culture model which allows us to study epiMT. Using this model, we identify novel epiMT regulators. Because EMT is also involved in pathological remodeling, application of an epiMT stimulator should be transient and local. Therefore, we describe a method to locally administer these factors to the injured mouse heart. Show less
Cell-based in vitro developed human skin equivalents facilitate screenings of compounds for therapeutic potential or toxicity and enable scientific research expanding knowledge on skin physiology... Show moreCell-based in vitro developed human skin equivalents facilitate screenings of compounds for therapeutic potential or toxicity and enable scientific research expanding knowledge on skin physiology and pathophysiology. Human skin equivalents resemble key features of native human skin, including the dermal and epidermal architecture. However, a limitation of human skin equivalents is the altered lipid barrier formation, which leads to a decreased barrier functionality. This could be induced by suboptimal cell culture conditions or the different cell microenvironment. The primary aim of this dissertational research was to enhance the morphogenesis and barrier formation of human skin equivalents to better mimic that of native human skin. The results indicate that modification of the dermal extracellular matrix by the biopolymer chitosan enhanced epidermal morphogenesis and barrier formation. Furthermore, by better resembling native skin conditions in vitro, primarily through a reduction in oxygen level, the epidermal morphogenesis and lipid barrier formation was improved. Finally, using a combinatory approach of optimized cell culture conditions and enhanced cell culture medium, the epidermal morphogenesis and barrier formation of human skin equivalents resembled that of native human skin more closely. Show less
