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The main problem of currently used xenogeneic biological heart valves is the development of degenerative changes leading to valve failure. Reoperation is required in approximately 65% of patients at 15 years after implantation. The challenge of heart valve tissue engineering is to create a new type of biological prosthesis for clinical use. The aim of our study is to construct a living autologous human pericardial heart valve that will have optimal mechanical properties and a similar histological structure as the normal aortic heart valve. Three leaflet heart valve constructs made from human pericardium were attached onto a plastic holder and cultured under dynamic conditions for up to four weeks. After this time conditioned pericardial samples were compared to control unconditioned pericardial samples from the same patient and to that of the normal aortic heart valve. Histological, immunohistochemical and biomechanical assessments were performed. Pericardial interstitial cells (PICs) are able to respond to mechanical stresses by proliferating and differentiating into an active (myofibroblast-like) phenotype and are able to produce new extracellurar matrix (ECM). A threefold increase in PIC number and a twofold increase in smooth muscle actin (SMA) positive cells was observed after dynamic conditioning. These measurements were statistically significant (p

The objective of our study was to compare the histological structure and cellular organization of autologous human pericardium to that of the human aortic heart valve. Collagen, elastin and glycosaminoglycans are responsible for the mechanical properties of aortic heart valve leaflets. Aortic valve leaflets are composed primarily of collagen representing 50% of total extracellular matrix (ECM). The main collagen types in the aortic heart valve are collagen I (74% of total collagen) and collagen III (24% of total collagen). Elastin represents 13% and is responsible for the elastic properties of the valve leaflet. Collagen has a specific architecture that endows heart valve tissue with the ability to withstand circulatory forces over the course of a lifetime. Its fiber orientation, density and cell associations are very important for this purpose. Normal aortic heart valves were obtained during heart transplantation and compared to autologous human pericardium before and after dynamic conditioning using classical histological assessment, immunohistochemical analysis and confocal microscopy. The architecture of pericardial tissue is very similar to that of the normal aortic heart valve possessing well organized collagen fibers with embedded pericardial interstitial cells (PICs) forming a three dimensional network. Instead of the trilaminar histological organization present in the aortic heart valve, the pericardium possesses one layer whose densely packed collagen bundles closely resemble that of the lamina fibrosa of the native aortic heart valve by confocal microscopy. Elastin fibers are evenly distributed throughout the entire thickness of the pericardium in comparison to the specialized elastin containing layer in the lamina ventricularis of the aortic heart valve. PICs are also evenly distributed throughout the pericardium. In the inner pericardial layer facing the heart these cells have a more spindle-like shape similar to that of valvular interstitial cells (VICs) in the lamina fibrosa, while in the outer part of the pericardium these cells have a more spread-out cytoplasmic morphology interacting with more loosely distributed collagen bundles. Like in the aortic heart valve, PICs show cell-cell interactions in addition to cell-matrix interactions. Our study confirmed similarities in the cellular and ECM organization of human pericardium and the native aortic heart valve. It may be concluded that human autologous pericardium may be a favorable tissue for heart valve replacement. Autologous pericardial tissue may also avoid a negative immune system response that could adversely affect recipient graft uptake and downstream ECM remodeling events.