Title: Tissue engineering van hartkleppen: groei- en differentiatiedynamiek van cardiovasculaire weefselontwikkeling
Other Titles: Cardiac Valve Tissue Engineering: Growth en Differentiation Dynamics in Cardiovascular Tissue Development Final
Authors: Lebacq, An; S0112341
Issue Date: 11-May-2009
Abstract: Cardiovascular diseases have a high impact on quality of life and health care expenses in Western societies. Heart valve disease in particular, h as led to about 400 000 heart valve replacements worldwide in 2004. Mech anical or bioprosthetic valves are used as replacements, each presenting specific disadvantages. Generally, research has been focusing on the im provement of current valve prostheses by diminishing degeneration and ca lcification. Additionally, in the last decade, research effort is direct ed towards the development of tissue engineered heart valves to overcome major drawbacks of prostheses and to present a solution for children. Although most of the current research in heart valve tissue engineering is focusing on in vitro approaches, our laboratory has turned its att ention to the alternative field of in vivo tissue engineering where t he animal or patientÂ’s own body is used as a unique in vivo maturatio n environment. To understand the cellular processes occurring in the nat ural environment of the peritoneal cavity, a location we have used for c reating preseeded functional tissue engineered heart valves, we have stu died the cellular differentiation properties of intraperitoneally implan ted biological matrices in rat, followed by the application of a specifi c time point of intraperitoneal coating, namely three days, in tissue en gineered heart valves in sheep. These valves were shown to be functional on the long term (up to five months), however, due to an excessive pres ence of cells with contractile properties as compared to native heart va lves and causing approximately 15% valve leaflet shrinkage and mild regu rgitation, we changed our approach and embarked on the third and final p art of the project where we have studied gene expression of cardiovascul ar tissues in both a different regional field, namely semilunar heart va lves and aortae and a different temporal window, namely neonatal and adu lt tissues. One of the requirements of tissue engineered blood vessels and heart val ves is the capacity to remodel or grow. This is especially important for children, now requiring several valve replacement surgeries during thei r youth. Heart valves have a very specific morphology and are shaped by an intricate developmental process. Although early valve development has been largely elucidated, the following cellular and extracellular matri x maturation, remodelling and growth mechanisms that give rise to the un ique valve morphology and cell composition remain unexplored. Interestin gly, the heart continues to develop after birth to adjust to growth-depe ndent changes in both shape and vascular pressure. There are also indica tions that a similar phenomenon exists in the vasculature. Therefore, in this project, we have explored this early neonatal cardiovascular tissu e gene expression, to discover processes, pathways and molecules that ca n be used in future clinical applications, such as the in vivo follow -up of cardiovascular prostheses and development of tissue engineered ca rdiovascular constructs, coated with specific molecules, thus creating a bioactive matrix stimulating correct cell attraction, attachment and di fferentiation. Out of a very stringent statistical analysis of the differential gene ex pression data, we obtained eight different groups of cardiovascular mark ers: neonatal valve, neonatal cardiovascular, neonatal aorta, general va lve, general aorta, adult valve, adult cardiovascular and adult valve ma rkers. Three groups of cardiovascular markers were particularly interest ing in the context of this project, namely neonatal valve, neonatal card iovascular and neonatal aorta markers, especially in view of future clin ical applications of cardiovascular tissue engineering. These groups rep resent gene lists of 13, 7 and 10 genes, respectively. One molecule drew our particular attention, namely Tenascin C and its pr esence was confirmed on mRNA and protein level in neonatal cardiovascula r tissue. Interestingly, Tenascin C protein was also found to be present in remodelling tissue engineered heart valves and therefore it represen ts an appealing candidate for clinical applications, such as in vivo non-invasive evaluation of tissue engineered heart valve prostheses, or cardiovascular prostheses in general, and the development of a bioactive cardiovascular prosthetic matrix.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Experimental Cardiac Surgery
Spin-off & Innovation
Technology Transfer - miscellaneous

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