These findings suggest that tissue valve calcification is determined by many independent factors, which can be identified by using adolescent sheep as a preclinical in vivo model.
Evidence has been gathered that biomechanical factors have a significant impact on cell differentiation and behavior in in vitro cell cultures. The aim of this bioreactor is to create a physiological environment in which tissue engineered (TE) aortic valves seeded with human cells can be cultivated during a period of several days. The bioreactor consists of 2 major parts: the left ventricle (LV) and the afterload consisting of a compliance, representing the elastic function of the large arteries, and in series a resistance, mimicking the arterioles and capillaries. The TE aortic valve is placed between the LV and the compliance. With controllable resistance, compliance, stroke volume and frequency, and hydrodynamic conditions can be changed over a wide physiological range. This study resulted in a prototype of a compact pulsatile flow system for the creation of TE aortic valves. In addition a biocompatibility study of the used materials is performed.
To improve the durability of stentless valves without losing their excellent hemodynamic function, a new-generation auto-xenograft was developed and evaluated. A piece of vein was harvested from 3 juvenile sheep 6 weeks before implantation of the valve. Endothelial cells from the vein material were cultivated and used to reendothelialize a decellularized porcine pulmonary valve. The tissue-engineered valve was implanted into the right ventricular outflow tract of the juvenile sheep. It was explanted after 100 days and assessed macroscopically as well as by x-ray, light microscopy (hematoxylin and eosin staining and von Kossa staining), and scanning electron microscopy. Calcium content of the cusps was determined quantitatively by atomic absorption spectrometry. The sheep implanted with the valve recovered quickly without any problems during the observation period. X-ray examination of the 3 explanted valves showed no cusp calcification, which was confirmed by histological study. Atomic absorption spectrometry showed low tissue calcium content. A clinical safety and feasibility trial with an allograft valve prepared the same way showed excellent short-term results in 6 patients.
At present the involvement of cardiac valve interstitial cells (VICs) in growth, repair, and tissue engineering is understudied. Therefore, this study aims at characterizing ovine VICs in order to provide a solid base for tissue engineering of heart valves. Ovine ICs of the four heart valves were isolated by the explant outgrowth method and expanded in vitro up to passage 5. Vimentin and collagen I gene expression from freshly isolated or cultured ICs was measured by reverse transcriptase-polymerase chain reaction. Immunocytochemical stainings of vimentin, alpha-smooth muscle actin (ASMA), smooth muscle myosin, and procollagen I were performed on aortic VICs. In addition, migration and extracellular matrix deposition were studied in vitro in aortic VICs. ICs show stable vimentin and collagen I expression in culture. Expression is approximately doubled in cultured ICs compared with fresh isolates. More than 95% of ICs in each passage stain for vimentin and procollagen I. Freshly isolated ICs are ASMA and myosin negative, but ICs in culture partially stain for these contractile markers. ICs have stable matrix production for up to five passages, associated with stable migration of the cells. We conclude that ovine valve interstitial cells undergo phenotypic modulation to activated myofibroblasts under culture conditions but retain stable matrix production.
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