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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.

Author information

1
Department for Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Germany. Electronic address: sarikouch.samir@mh-hannover.de.
2
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Germany.
3
Department for Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Germany.
4
Department of Cardiac Surgery, Medical University of Vienna, Austria.
5
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).
6
Department of Histopathology, Royal Brompton and Harefield Hospital, London, United Kingdom.
7
Department for Pediatric Cardiology and Intensive Care, Hannover Medical School, Germany.

Abstract

BACKGROUND:

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.

METHODS:

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%.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Heart valve disease; decellularization; recellularization; tissue engineering

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