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,1
* Laboratoire d’Organogénèse Expérimentale, Hôpital du Saint-Sacrement du CHA, 1050, chemin Sainte-Foy, Québec Canada G1S 4L8 and Department of Surgery, Laval University, Québec, Canada; and
Laboratoire de Pharmacologie et Physico-Chimie des Intéractions Cellulaires et Moléculaires, Université Louis Pasteur de Strasbourg, Faculté de Pharmacie, UMR CNRS 7034, BP 24, 67401 Illkirch-Cedex, France
2Correspondence: Laboratoire d’Organogenèse Expérimentale, Hôpital du Saint-Sacrement du CHA, 1050, chemin Sainte-Foy, Québec, Canada G1S 4L8. E-mail: Lucie.germain{at}chg.ulaval.ca
Our method for producing tissue-engineered blood vessels based exclusively on the use of human cells, i.e., without artificial scaffolding, has previously been described (1). In this report, a tissue-engineered vascular media (TEVM) was specifically produced for pharmacological studies from cultured human vascular smooth muscle cells (VSMC). The VSMC displayed a differentiated phenotype as demonstrated by the re-expression of VSMC-specific markers and actual tissue contraction in response to physiological stimuli. Because of their physiological shape and mechanical strength, rings of human TEVM could be mounted on force transducers in organ baths to perform standard pharmacological experiments. Concentration-response curves to vasoconstrictor agonists (histamine, bradykinin, ATP, and UTP) were established, with or without selective antagonists, allowing pharmacological characterization of receptors (H1, B2, and P2Y1, and pyrimidinoceptors). Sustained agonist-induced contractions were associated with transient increases in cytosolic Ca2+ concentration, suggesting sensitization of the contractile machinery to Ca2+. ATP caused both Ca2+ entry and Ca2+ release from a ryanodine- and caffeine-sensitive store. Increased cyclic AMP or cyclic GMP levels caused relaxation. This human TEVM displays many of functional characters of the normal vessel from which the cells were originally isolated, including contractile/relaxation responses, cyclic nucleotide sensitivity, and Ca2+ handling mechanisms comparable to those of the normal vessel from which the cells were originally isolated. These results demonstrate the potential of this human model as a versatile new tool for pharmacological research.—L’Heureux, N., Stoclet, J.-C., Auger, F. A., Lagaud, G. J.-L., Germain, L., Andriantsitohaina, R. A human tissue-engineered vascular media: a new model for pharmacological studies of contractile responses.
Key Words: tissue engineering • blood vessel • pharmacology • calcium • purinoceptors • cyclic nucleotides • contraction
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