Fulltext

Tissue-engineered vascular graft remodeling in a growing lamb model: expression of matrix metalloproteinases

Cummings, Ian ; George, Sarah ; Kelm, Jens ; Schmidt, Doerthe ; Emmert, Maximilian Y. ; Weber, Benedikt ; Zünd, Gregor ; Hoerstrup, Simon P.

In: European Journal of Cardio-Thoracic Surgery, 2012, vol. 41, no. 1, p. 167-172

Ajouter à la liste personnelle
    Titre
    • Tissue-engineered vascular graft remodeling in a growing lamb model: expression of matrix metalloproteinases
    Auteur
    • Cummings, Ian. Swiss Center for Regenerative Medicine, University Hospital and University Zurich, Zurich, Switzerland
    • George, Sarah. Bristol Heart Institute, Bristol Royal Infirmary, Bristol, UK
    • Kelm, Jens. Swiss Center for Regenerative Medicine, University Hospital and University Zurich, Zurich, Switzerland
    • Schmidt, Doerthe. Swiss Center for Regenerative Medicine, University Hospital and University Zurich, Zurich, Switzerland
    • Emmert, Maximilian Y.. Swiss Center for Regenerative Medicine, University Hospital and University Zurich, Zurich, Switzerland
    • Weber, Benedikt. Swiss Center for Regenerative Medicine, University Hospital and University Zurich, Zurich, Switzerland
    • Zünd, Gregor. Swiss Center for Regenerative Medicine, University Hospital and University Zurich, Zurich, Switzerland
    • Hoerstrup, Simon P.. Swiss Center for Regenerative Medicine, University Hospital and University Zurich, Zurich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • European Journal of Cardio-Thoracic Surgery, 2012, vol. 41, no. 1, p. 167-172. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:297555
    Summary
    OBJECTIVES We have previously demonstrated the functionality and growth of autologous, living, tissue-engineered vascular grafts (TEVGs) in long-term animal studies. These grafts showed substantial in vivo tissue remodeling and approximation to native arterial wall characteristics. Based on this, in vitro and in vivo matrix metalloproteinase (MMP) activity of TEVGs is investigated as a key marker of matrix remodeling. METHODS TEVGs fabricated from biodegradable scaffolds (polyglycolic-acid/poly-4-hydroxybutyrate, PGA/P4HB) seeded with autologous vascular cells were cultured in static and dynamic in vitro conditions. Thereafter, TEVGs were implanted as pulmonary artery replacements in lambs and followed up for 2 years. Gelatin gel zymography to detect MMP-2 and -9 was performed and collagen content quantified (n=5). Latent (pro) and active MMP-2 and -9 were detected. RESULTS Comparable levels of active MMP-9 and pro-MMP-2 were detected in static and dynamic culture. Higher levels of active MMP-2 were detected in dynamic cultures. Expression of MMP-2 and -9 was minimal in native grafts but was increased in implanted TEVG. Pro-MMP-9 was expressed 20 weeks post implantation and persisted up to 80 weeks post implantation. Collagen content in vitro was increased in dynamically conditioned TEVG as compared with static constructs and was increased in vivo compared with the corresponding native pulmonary artery. CONCLUSIONS MMPs are up-regulated in vitro by dynamic culture conditions and could contribute to increased matrix remodeling, native analogous tissue formation and functional growth of TEVGs in vivo. Monitoring of MMP activity, for example, by molecular imaging techniques, may enable the non-invasive assessment of functional tissue quality in future clinical tissue-engineering applications