Abstract
The creation of living heart valve replacements via tissue engineering is actively being pursued by many research groups. Numerous strategies have been described, aimed either at culturing autologous living valves in a bioreactor (in vitro) or inducing endogenous regeneration by the host via resorbable scaffolds (in situ). Whereas a lot of effort is being invested in the optimization of heart valve scaffold parameters and culturing conditions, the pathophysiological in vivo remodeling processes to which tissue-engineered heart valves are subjected upon implantation have been largely under-investigated. This is partly due to the unavailability of suitable immunohistochemical tools specific to sheep, which serves as the gold standard animal model in translational research on heart valve replacements. Therefore, the goal of this study was to comprise and validate a comprehensive sheep-specific panel of antibodies for the immunohistochemical analysis of tissue-engineered heart valve explants. For the selection of our panel we took inspiration from previous histopathological studies describing the morphology, extracellular matrix composition and cellular composition of native human heart valves throughout development and adult stages. Moreover, we included a range of immunological markers, which are particularly relevant to assess the host inflammatory response evoked by the implanted heart valve. The markers specifically identifying extracellular matrix components and cell phenotypes were tested on formalin-fixed paraffin-embedded sections of native sheep aortic valves. Markers for inflammation and apoptosis were tested on ovine spleen and kidney tissues. Taken together, this panel of antibodies could serve as a tool to study the spatiotemporal expression of proteins in remodeling tissue-engineered heart valves after implantation in a sheep model, thereby contributing to our understanding of the in vivo processes which ultimately determine long-term success or failure of tissue-engineered heart valves.
Highlights
Valvular heart disease is a major health problem
Mimicking the sophisticated trilayered structure of the native valve, including a well-organized anisotropic collagen and elastin network populated with quiescent valvular interstitial cells (VICs), requires a thorough understanding of valvular developmental and biomechanical remodeling processes [26, 27]
The immunohistochemical analysis of explanted tissue engineering (TE) heart valves in preclinical studies is typically limited to a few antibody stainings assessing VIC activation and endothelial coverage (e.g., α-SMA and CD31)
Summary
Valvular heart disease is a major health problem. Heart valve tissue engineering (TE) strategies aim to create autologous, living heart valves with the potential for growth and remodeling to replace the malfunctioning heart valve. Since approximately two decades ago, several TE strategies have been actively pursued to create living heart valve replacements in vitro, using a variety of cell sources, scaffold types and fabrication methods [1,2,3,4,5,6,7,8,9,10,11]. The host immune response evoked by a TE heart valve after implantation is perhaps the most crucial determinant of successful valve integration This is even more important for in situ TE strategies, which rely on triggering a favorable inflammatory response upon implantation in order to induce a regenerative cascade [13, 28, 29]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
