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J Thorac Cardiovasc Surg 2006;131:843-852
© 2006 The American Association for Thoracic Surgery

Evolving Technology

Decellularized heart valve as a scaffold for in vivo recellularization: Deleterious effects of granulocyte colony-stimulating factor

Francis Juthier, MD a , b , André Vincentelli, MD, PhD a , b , * , Julien Gaudric, MD a , b , Delphine Corseaux, PhD a , Olivier Fouquet, MD a , b , Christine Calet, MD a , b , Thierry Le Tourneau, MD, PhD a , Valérie Soenen, BS c , Christophe Zawadzki, BS a , c , Olivier Fabre, MD a , b , Sophie Susen, MD a , c , Alain Prat, MD a , b , Brigitte Jude, MD, PhD a , c

a Institut National de la Santé et de la Recherche Médicale (Inserm) ERI-9, Faculté de Médecine, Lille, France
b Centre Hospitalier Régional Universitaire de Lille, Clinique de Chirurgie Cardiovasculaire, Lille, France
c Institut d'Hématologie-Transfusion, Lille, France

Received for publication August 5, 2005; revisions received November 20, 2005; accepted for publication November 28, 2005.

* Address for reprints: André Vincentelli, MD, PhD, Clinique de Chirurgie Cardio-vasculaire, Hôpital Cardiologique, 59037 Lille cedex (Email: a-vincentelli{at}chru-lille.fr).

BACKGROUND: Autologous recellularization of decellularized heart valve scaffolds is a promising challenge in the field of tissue-engineered heart valves and could be boosted by bone marrow progenitor cell mobilization. The aim of this study was to examine the spontaneous in vivo recolonization potential of xenogeneic decellularized heart valves in a lamb model and the effects of granulocyte colony-stimulating factor mobilization of bone marrow cells on this process.

METHODS: Decellularized porcine aortic valves were implanted in 12 lambs. Six lambs received granulocyte colony-stimulating factor (10 µg · kg–1 · d–1 for 7 days, granulocyte colony-stimulating factor group), and 6 received no granulocyte colony-stimulating factor (control group). Additionally, nondecellularized porcine valves were implanted in 5 lambs (xenograft group). Angiographic and histologic evaluation was performed at 3, 6, 8, and 16 weeks.

RESULTS: Few macroscopic modifications of leaflets and the aortic wall were observed in the control group, whereas progressive shrinkage and thickening of the leaflets appeared in the granulocyte colony-stimulating factor and xenograft groups. In the 3 groups progressive ovine cell infiltration (fluorescence in situ hybridization) was observed in the leaflets and in the adventitia and the intima of the aortic wall but not in the media. Neointimal proliferation of {alpha}-actin–positive cells, inflammatory infiltration, adventitial neovascularization, and calcifications were more important in the xenograft and the granulocyte colony-stimulating factor groups than in the control group. Continuous re-endothelialization appeared only in the control group.

CONCLUSION: Decellularized xenogeneic heart valve scaffolds allowed partial autologous recellularization. Granulocyte colony-stimulating factor led to accelerated heart valve deterioration similar to that observed in nondecellularized xenogeneic cardiac bioprostheses.

Abbreviations and Acronyms BM = bone marrow; G-CSF = granulocyte colony-stimulating factor; VWF = Von Willebrand Factor




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