In vivo repopulation of xenogeneic and allogeneic acellular valve matrix conduits in the pulmonary circulation.
BACKGROUND
Approaches to in vivo repopulation of acellularized valve matrix constructs have been described recently. However, early calcification of acellularized matrices repopulated in vivo remains a major obstacle. We hypothesised that the matrix composition has a significant influence on the onset of early calcification. Therefore, we evaluated the calcification of acellularized allogenic ovine (AVMC) and xenogenic porcine (XVMC) valve matrix conduits in the pulmonary circulation in a sheep model.


METHODS
Porcine (n = 3) and sheep (n = 3) pulmonary valve conduits were acellularized by trypsin/EDTA digestion and then implanted into healthy sheep in pulmonary valve position using extracorporeal bypass support. Transthoracic echocardiography (TTE) was performed at 12 and 24 weeks after the implantation. The animals were sacrificed at week 24 or earlier when severe calcification of the valve conduit became evident by TTE. The valves were examined histologically and biochemically.


RESULTS
All AVMC revealed severe calcification after 12 weeks with focal endothelial cell clustering and no interstitial valve tissue reconstitution. In contrast, after 24 weeks XVMC indicated mild calcification on histologic examination (von Kossa staining) with histologic reconstitution of valve tissue and confluent endothelial surface coverage. Furthermore, immunohistologic analysis revealed reconstitution of surface endothelial cell monolayer (von Willebrand factor), and interstitial myofibroblasts (Vimentin/Desmin).


CONCLUSIONS
Porcine acellularized XVMC are resistant to early calcification during in vivo reseeding. Furthermore, XVMC are repopulated in vivo with valve-specific cell types within 24 weeks resembling native valve tissue.
Leyh
Rainer G
RG
Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany. leyh@thg.mh-hannover.de
Wilhelmi
Mathias
M
Rebe
Philip
P
Fischer
Stefan
S
Kofidis
Theo
T
Haverich
Axel
A
Mertsching
Heike
H
D000818:Animals; D001705:Bioprosthesis; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D018618:Echocardiography, Doppler, Color; D004727:Endothelium / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology; D006350:Heart Valve Prosthesis / Q000009:adverse effects; D019918:Heart Valve Prosthesis Implantation; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis; D009206:Myocardium / Q000473:pathology; D011664:Pulmonary Valve / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery*; D012756:Sheep; D013552:Swine; D023822:Tissue Engineering; D014841:von Willebrand Factor / Q000032:analysis
D007381:Intermediate Filament Proteins; D014841:von Willebrand Factor