Biological fate of tissue-engineered porcine valvular conduits xenotransplanted in the sheep thoracic aorta.
The ideal prosthesis to replace the diseased human aortic valve is not yet available. We have previously shown that porcine acellular aortic-valve conduits, obtained by detergent-enzymatic method, display hemodynamic performances similar to those of their native counterparts. Hence, it seemed worthwhile to ascertain whether these tissue-engineered prostheses can be successfully xenotransplanted. Porcine acellular conduits, which immunocytochemistry demonstrated to lack MHC class I and II antigens, were implanted in the thoracic aorta of 9 sheep. Two animals died just after surgery, and the other 7 sheep were sacrificed 1 or 5 months after transplantation. A rather favorable outcome of the implant was observed in 4 sheep. In these animals, aortic valves remained pliable and coaptive, and the luminal surface of the conduits was endothelized just after one month from surgery. An intense inflammatory response was present at 1 month, and, although attennuated, it persisted for 5 months, located mainly between the tunica intima and media and at the border of the implant. Vimentin-positive and smooth muscle actin-positive myofibroblasts proliferated within tunica media and adventitia, and an obvious thickening of the tunica intima was also observed. Small vessels were seen in the adventitia, and elastic fibers were well-preserved in both the aorta wall and valve leaflets. In the cases of unfavorable outcome (3 of 7 survived sheep), implants were detached from the aorta recipient and surrounded by a connective mass that almost completely obstructed their lumen. These masses were composed of a fibromyxoid background where proliferating cells, resembling those occurring in human reactive myofibroblastic lesions (proliferative fascitis), were embedded. Collectively, these rather disappointing findings indicate that acellular valve conduits, obtained by the detergent-enzymatic method, are presently not suitable for clinical applications because of the persistent inflammatory response, which conceivably triggers overgrowth mechanisms that lead to implant failure.
Conconi
Maria Teresa
MT
Department of Pharmaceutical Sciences, University of Padua, I-35121 Padua, Italy.
Rocco
Francesco
F
Spinazzi
Raffaella
R
Tommasini
Mara
M
Valfrè
Carlo
C
Busetto
Roberto
R
Polesel
Elvio
E
Albertin
Giovanna
G
Dei Tos
Angelo
A
Iacopetti
Ilaria
I
Cecchetto
Attilio
A
Zussa
Claudio
C
Grigioni
Mauro
M
Parnigotto
Pier Paolo
PP
Nussdorfer
Gastone Giovanni
GG
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology* / Q000473:pathology / Q000601:surgery* / Q000648:ultrastructure; D001021:Aortic Valve / Q000166:cytology / Q000637:transplantation*; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D012756:Sheep; D013552:Swine; D023822:Tissue Engineering / Q000009:adverse effects*; D014183:Transplantation, Heterologous / Q000009:adverse effects* / Q000473:pathology; D016896:Treatment Outcome