Organ Culture of Porcine Mitral Valves as a Novel Experimental Paradigm

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Mitral valve diseases are prevalent disorders, but how these conditions develop is poorly understood. Organ culture systems offer the potential to investigate valve biology and pathology in vitro. The purpose of this research was to determine whether culture within an organ culture system preserves the normal valve phenotype. Porcine mitral valves cultured for 3 weeks in an organ culture system (n = 5) were characterized mechanically, biochemically and histologically and compared to freshly harvested (n = 7) and static culture valves (without mechanical stimulation, n = 6). The dynamic culture system provided mechanical stimulation through physiologically relevant pressures and flow rates. The organ culture system maintained function and was free of contamination, but experienced an increase in regurgitant flow, over the culture duration. The static culture valves had lower DNA content (cellularity) and radial tensile modulus, and greater thickness and hydration compared with the fresh valves, whereas the dynamic culture valves better preserved these characteristics. Both groups of cultured valves had lower tensile moduli of the chordae tendineae compared to chordae from freshly harvested valves, and both groups demonstrated a reduction of glycosaminoglycans and proteoglycans, particularly hyaluronan and versican. The investigated organ culture system was able to maintain several aspects, but not all aspects, of normal mitral valve mechanics and microstructure. Challenges in maintaining normal forward flow likely altered the valve hemodynamics, and will require further refinement of the organ culture system. Nonetheless, organ culture systems offer considerable promise as a new experimental paradigm for studies of valve biology and pathology.