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Ann Thorac Surg. 2019 Mar 27. pii: S0003-4975(19)30414-X. doi: 10.1016/j.athoracsur.2019.02.058. [Epub ahead of print]

Early Insight into In-vivo recellularization of cell-free allogenic heart valves.

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Department for Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Germany. Electronic address:
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Germany.
Department for Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Germany.
Department of Cardiac Surgery, Medical University of Vienna, Austria.
Institute of Pathology, Hannover Medical School, Germany; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), The German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL).
Department of Histopathology, Royal Brompton and Harefield Hospital, London, United Kingdom.
Department for Pediatric Cardiology and Intensive Care, Hannover Medical School, Germany.



Unlike the vast amount of animal data available on the recellularization of allogenic decellularized heart valves (DHV), there have only been sporadic histological reports on such grafts in humans.


Two experienced cardiac pathologists independently evaluated human specimens obtained during re-operation between 12/2010 and 4/2017 DHV in 7 categories following automated staining (scores 0-6) in comparison to published data. An optimal result of 42 points was classified as 100%.


364 DHV, 236 pulmonary (DPH) and 128 aortic (DAH) were implanted, freedom from explantation was 96.1% (DAH) and 98.7% (DPH). Re-operations were due to (suspected) endocarditis in 5/11, stenosis either at subvalvular/valvular /supravalvular level in 3/11, planned staged re-operation in 2/11 and 1 heart transplant. Good reader agreement was reflected by an inter-agreement weighted Kappa of 0.783 (0.707-0.859, 95% CI). The relative histological score in non-endocarditis cases was 76% (±4.3, max.81%). Intracellular pro-collagen type 1 production was found in recipient mesenchymal cells within the transplanted grafts. In endocarditis cases the histological score was significantly lower with 48% (±7.3, min.41%, p=0.0004) due to leucocyte infiltration and matrix degradation. 1 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 recellularisation.


Significant in-vivo recellularization with non-inflammatory cells was observed in this study. Spontaneous recellularization appears to require multiple months, which correspondingly has an impact on size selection for growing patients.


Heart valve disease; decellularization; recellularization; tissue engineering

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