Early Insight Into In Vivo Recellularization of Cell-Free Allogenic Heart Valves

Sarikouch, Samir; Theodoridis, Kaolina; Hilfiker, Andres; Boethig, Dietmar; Laufer, Günther; Andreas, Martin; Cebotari, Serghei ORCID; Tudorache, Igor; Bobylev, Dmitry; Neubert, Lavinia; Teiken, Kristin; Robertus, Jan Lukas; Jonigk, Danny; Beerbaum, Philipp ORCID; Haverich, Axel; Horke, Alexander

BACKGROUND: Unlike the vast amount of animal data available on the recellularization of allogenic decellularized heart valves (DHVs), there have only been sporadic histologic reports on such grafts in humans. METHODS: Two experienced cardiac pathologists independently evaluated human specimens obtained during reoperation between December 2010 and April 2017 DHVs in seven categories after automated staining (scores: 0 to 6) in comparison with published data. An optimal result of 42 points was classified as 100%. RESULTS: We found that 364 DHVs, 236 decellularized pulmonary homografts (DPHs), and 128 decellularized aortic homografts (DAHs) were implanted, and freedom from explantation was 96.1% (DAH) and 98.7% (DPH). Reoperations were because of (suspected) endocarditis in 5 of 11 patients, stenosis at the subvalvular or valvular or supravalvular level in 3 of 11 patients, planned staged reoperation in 2 of 11 patients, and 1 heart transplantation. Good reader agreement was reflected by an interagreement weighted kappa of 0.783 (95% confidence interval: 0.707 to 0.859). The relative histologic score in nonendocarditis specimens was 76% +/- 4.3% (maximum 81%). Intracellular procollagen type 1 production was found in recipient mesenchymal cells within the transplanted grafts. In endocarditis specimens the histologic score was significantly lower with 48% +/- 7.3% (minimum 41%, p = 0.0004) because of leucocyte infiltration and matrix degradation. One DPH showed immune system-mediated graft failure. Grafts obtained during the first 12 months after implantation were not evenly repopulated with less recellularization in the inner parts; no difference was found between DAH and DPH with respect to extent of recellularization. CONCLUSIONS: Substantial in vivo recellularization with noninflammatory cells was observed in this study. Spontaneous recellularization appears to require multiple months, which correspondingly has an impact on size selection for growing patients


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Sarikouch, Samir / Theodoridis, Kaolina / Hilfiker, Andres / et al: Early Insight Into In Vivo Recellularization of Cell-Free Allogenic Heart Valves. 2019.

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