| dc.description.abstract | Stem cells are able to divide repeatedly and produce both new stem cells and differentiated cells, thereby ensuring a supply of new differentiated cells. In several traumas and diseases, cell losses in affected tissues are too severe to be regenerated by endogenous stem cells. In these cases, stem cell-based therapies could be applied to repair the damaged tissues, either by repopulating the tissue with new differentiated cells or by in vitro formation of tissue for transplantation (tissue engineering). Cardiovascular diseases are among the candidates for stem cell-based therapies. This thesis reviews possible applications of stem cells in coronary heart disease and heart valve disease.
Coronary heart disease is the major cause of death within the cardiovascular diseases. In this disease, a coronary artery that supplies the myocardium with oxygen becomes obstructed due to atherosclerosis. This leads to myocardial infarction and the death of the cardiomyocytes in the affected area. Since the heart is not able to regenerate the damaged tissue, the lost cardiomyocytes will be replaced by fibrous scar tissue, which is not contractile, thereby leading to a decrease in contractility, and thus function, of the heart. Stem cell-based therapies that are able to repopulate the damaged myocardial tissue with new cardiomyocytes would thus be extremely useful to prevent progression to heart failure after myocardial infarction. For the generation of cardiomyocytes, currently tree types of cells are studied: embryonic stem cells, which can be isolated from early embryos, adult stem cells, which can be isolated from adult tissues, and induced pluripotent stem cells, which resemble embryonic stem cells, but are generated from differentiated adult cells. When stimulating the different types of stem cells with the right factors, they are able to differentiate into cardiomyocytes. Experiments in animal models indicate possible beneficial effects of stem cell-derived cardiomyocyte transplantations after myocardial infarctions, but some major difficulties remain to be solved before such treatments can be applied in the clinic, most important being the survival of the transplanted cells and their integration in the damaged tissue. Besides the transplantation of in vitro generated cardiomyocytes, possibilities for the transplantation of in vitro engineered myocardial tissue are explored.
Although not occurring as much as coronary heart disease, heart valve disease is a significant cause of death within the cardiovascular diseases. In heart valve disease, malfunctioning heart valves lead to a decrease in pump function of the heart and thereby cause heart failure. Currently, heart valves are replaced with prostheses that know major complications and limitations. Therefore, possibilities are explored to produce patient-specific, living replacements from stem cells (tissue engineered heart valves). Experiments have shown that it is possible to engineer heart valves, but these heart valves were not yet able to withstand the in vivo mechanical stress. Therefore, improvements are required before clinical application of tissue engineered heart valves.
Taken together, it is still a long way to effective and safe application of stem cell-based therapies for cardiovascular diseases in the clinic and much more research is required to reach this goal. | |
