Decellularized heart valve as a scaffold for in vivo recellularization: deleterious effects of granulocyte colony-stimulating factor.
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 microg x kg(-1) x 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.


CONCLUSIONS
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.
Juthier
Francis
F
Institut National de la Santé et de la Recherche Médicale (Inserm) ERI-9, Faculté de Médecine, Lille, France.
Vincentelli
André
A
Gaudric
Julien
J
Corseaux
Delphine
D
Fouquet
Olivier
O
Calet
Christine
C
Le Tourneau
Thierry
T
Soenen
Valérie
V
Zawadzki
Christophe
C
Fabre
Olivier
O
Susen
Sophie
S
Prat
Alain
A
Jude
Brigitte
B
D000199:Actins / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000601:surgery; D001021:Aortic Valve / Q000473:pathology / Q000637:transplantation*; D001705:Bioprosthesis; D049109:Cell Proliferation; D003238:Connective Tissue / Q000473:pathology; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D007150:Immunohistochemistry; D007958:Leukocyte Count; D023421:Models, Animal; D018919:Neovascularization, Physiologic; D011994:Recombinant Proteins; D012756:Sheep; D023822:Tissue Engineering / Q000379:methods*; D014183:Transplantation, Heterologous; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014841:von Willebrand Factor / Q000276:immunology
D000199:Actins; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim