Développement à visée clinique d'une prothèse vasculaire décellularisée de faible diamètre produite par génie tissulaire

Authors: Tondreau, Maxime
Advisor: Auger, François A.Bolduc, Stéphane
Abstract: There is a clinical need for small-diameter vascular prostheses (< 6 mm), particularly for coronary and femoro-popliteal bypasses. Small-diameter synthetic vascular prostheses, comprising no endothelium, present an unacceptable risk of thrombotic occlusion. For this reason, it is preferable to use autologous vessels from the patients. The saphenous vein is the gold standard for most bypasses. However, many patients have diseased vessels or vessels that have already been used. For these reasons, the LOEX has developed a tissue-engineered blood vessel using the method of self-assembly. Such vessels have a long period of production and cannot be made in advance and stored. Moreover, obstacles slow down the realization of preclinical studies; indeed, given the use of human cells, either new autologous animal models must be developed or experimental animals must be immunosuppressed. The main objective of this thesis is to optimize a small-diameter tissue-engineered blood vessel in order to accelerate the translation from the laboratory to a clinical setting. Inspired by previous work, the studies presented in this thesis have focused on vessels produced from human dermal fibroblasts which were then decellularized. Since the immune response is mostly directed against cells and not against the extracellular matrix, the decellularization allows inter-individual and inter-species immunological compatibility. We have successfully implanted five out of six non-immunosuppressed rats for a period of 6 months. Explants presented cellular infiltrations suggesting the formation of a new media covered by a confluent endothelium. We have thereby shown that vessels of an appropriate length and diameter could be produced for clinical applications. These vessels were preserved for up to three months without showing any sign of mechanical degradation. We have also endothelialized such vessels that were conditioned for one week in a bioreactor. The process led to a compaction of the extracellular matrix and an increase in the ultimate tensile strength. In conclusion, the possibility of making the decellularized vessels in advance and to use them in various preclinical animal models could greatly accelerate the clinical translation from the laboratory to patients.
Document Type: Thèse de doctorat
Issue Date: 2015
Open Access Date: 24 April 2018
Permalink: http://hdl.handle.net/20.500.11794/27057
Grantor: Université Laval
Collection:Thèses et mémoires

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