title: Successful matrix guided tissue regeneration of decellularized pulmonary heart valve allografts in elderly sheep.
abstract: In vivo repopulation of decellularized allografts with recipient cells leads to a positive remodeling of the graft matrix in juvenile sheep. In light of the increasing number of heart valve replacements among older patients (>65 years), this study focused on the potential for matrix-guided tissue regeneration in elderly sheep. Pulmonary valve replacement was performed in seven-year old sheep using decellularized (DV), decellularized and CCN1-coated (RV), or decellularized and in vitro reendothelialized pulmonary allografts (REV) (n=6, each group). CCN1 coating was applied to support re-endothelialization. In vitro re-endothelialization was conducted with endothelial-like cells derived from peripheral blood. Echocardiograms of all grafts showed adequate graft function after implantation and at explantation 3 or 6 months later. All explants were macroscopically free of thrombi at explantation, and revealed repopulation of the allografts on the adventitial side of valvular walls and proximal in the cusps. Engrafted cells expressed vimentin, sm α-actin, and myosin heavy chain 2, while luminal cell lining was positive for vWF and eNOS. Cellular repopulation of valvular matrix demonstrates the capacity for matrix-guided regeneration even in elderly sheep but is not improved by in vitro endothelialization, confirming the suitability of decellularized matrix for heart valve replacement in older individuals.
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany; Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Karolina
authors.initials: K
authors.lastname: Theodoridis
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany; Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Tudorache
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany; Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Calistru
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany; Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Serghei
authors.initials: S
authors.lastname: Cebotari
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany; Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Meyer
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Samir
authors.initials: S
authors.lastname: Sarikouch
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bara
authors.affiliation: Institute of Anatomy, University of Veterinary Medicine Hannover, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Brehm
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany; Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany; Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany. Electronic address: hilfiker.andres@mh-hannover.de.
authors.forename: Andres
authors.initials: A
authors.lastname: Hilfiker
mesh_terms: D064591:Allografts; D000818:Animals; D001705:Bioprosthesis; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D048091:Guided Tissue Regeneration / Q000379:methods; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation / Q000379:methods; D011664:Pulmonary Valve / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D012038:Regeneration; D012756:Sheep; D023822:Tissue Engineering
keywords: Decellularization; Endothelial-like cells; Heart valve replacement; Matrix-guided tissue regeneration; Tissue engineering