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European Heart Journal Advance Access originally published online on January 23, 2007
European Heart Journal 2007 28(11):1389-1396; doi:10.1093/eurheartj/ehl422
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

In vivo cellularization of a cross-linked matrix by intraperitoneal implantation: a new tool in heart valve tissue engineering

Geofrey De Visscher*, Ilse Vranken, An Lebacq, Christiaan Van Kerrebroeck, Javier Ganame, Erik Verbeken and Willem Flameng

Laboratory for Experimental Cardiac Surgery, Department of Cardiovascular Diseases, Katholieke Universiteit Leuven, Minderbroedersstraat 17, 3000 Leuven, Belgium

Received 21 April 2006; revised 26 October 2006; accepted 10 November 2006; online publish-ahead-of-print 23 January 2007.

* Corresponding author. Tel: +32 16 33 71 20; fax: +32 16 33 71 22. E-mail address: geofrey.devisscher{at}med.kuleuven.be

Aim: To use in vivo instead of in vitro cell seeding in heart valve tissue engineering.

Methods and results: Intraperitoneally preseeded, photo-oxidized bovine pericardial pulmonary valve constructs (group 1) were compared with non-preseeded constructs (group 2) implanted in sheep. All valves functioned normally and were macroscopically intact at explantation [1 week (n = 6) and 1 month (n = 6) in each group], except for one thrombosed leaflet in a group-2 valve at 1 month. Almost 10-fold higher neomatrix deposition and doubling of the leaflet thickness were found in group 1 vs. 2 (P < 0.05). A concomitant significant decrease in leaflet length (15%) was found at 1 month in group 1. The total cross-sectional surface and total amount of collagen of the original matrix remained unchanged in both groups at all times. Immunohistochemistry showed a low immune response, stem/progenitor cell infiltration, appropriated differentiation, and spontaneous endothelialization of the valves. Significantly, increased re-cellularization was found after IP preseeding compared with spontaneous seeding: cell coverage of the leaflet was 71–100 vs. 8–26% (P < 0.05), respectively.

Conclusion: Complete re-cellularization can be obtained by IP preseeding of an acellularized cross-linked matrix. Well-functioning valve constructs show cellularization and differentiation into myofibroblast phenotype and concomitant neomatrix deposition.

Key Words: Tissue engineering • Endogenous seeding • Heart valve

This paper was guest edited by Prof. Julie H. Campbell, University of Queensland, Australia


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