Response of Macrophage-Like U937 Cells to Decellularized Tissue Heart Valve Materials

Background and aim of the study: Decellularized materials, which represent a popular option for a variety of applications in regenerative medicine, including bioprosthetic heart valves, offer the opportunity to study cellular responses to extracellular matrix biochemistry and architecture. The study aim was to investigate the response of U937 macrophage-like cells (a model of the monocyte-derived macrophage, the pivotal cell to the initial and chronic cellular responses to implanted biomaterials) to, decellularized bovine pericardium, to explore its expected biological performance in vivo, and to predict any adverse reactions in clinical trials. Methods: Differentiated U937 cells were cultured on three surfaces: decellularized bovine pericardium (DBP); polydimethylsiloxane (PDMS); and tissue-culture polystyrene (TCPS). Cell lysates were analyzed for DNA (to determine cell attachment and viability), esterase (as a marker of degradative potential) and acid phosphatase activity (as a marker of the innate immune response). Cell morphology was also compared using confocal and scanning electron microscopy. Results: U937 cells cultured on DBP were less spread and had less multinucleation than cells on either control polymer. No significant differences in DNA amount were observed between the substrates at each time point. In addition, cells cultured on DBP contained less acid phosphatase and esterase activity than cells on TCPS (p <0.05). Conclusion: The study results suggested that U937 cells seeded onto DBP reacted with an altered, more mild, foreign body response than cells cultured on either PDMS or TCPS. This U937 cell model provides evidence that the response of macrophages to decellularized materials is not initially aggressive. The present study served as a first step in elucidating the biological mechanisms by which tissue-derived valve replacements fail in the host - an understanding that may direct a more rational design of valvular and decellularized materials.