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Ann Thorac Surg 2003;75:1457-1463
© 2003 The Society of Thoracic Surgeons


Original article: cardiovascular

In vivo repopulation of xenogeneic and allogeneic acellular valve matrix conduits in the pulmonary circulation

Rainer G. Leyh, MDa*, Mathias Wilhelmi, MDa, Philip Rebe, MDa, Stefan Fischer, MDa, Theo Kofidis, MDa, Axel Haverich, MD, PhDa, Heike Mertsching, PhDb

a Division of Thoracic and Cardiovascular Surgery, Hannover Medical School Hanover Germany
b Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover, Germany

* Address reprint requests to Dr Leyh, Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Carl Neuberg St. 1, 30623 Hannover, Germany
e-mail: leyh{at}thg.mh-hannover.de

Presented at the Thirty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2002.

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.




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