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Human tissue-engineered blood vessels for adult arterial revascularization

Abstract

There is a crucial need for alternatives to native vein or artery for vascular surgery. The clinical efficacy of synthetic, allogeneic or xenogeneic vessels has been limited by thrombosis, rejection, chronic inflammation and poor mechanical properties. Using adult human fibroblasts extracted from skin biopsies harvested from individuals with advanced cardiovascular disease, we constructed tissue-engineered blood vessels (TEBVs) that serve as arterial bypass grafts in long-term animal models. These TEBVs have mechanical properties similar to human blood vessels, without relying upon synthetic or exogenous scaffolding. The TEBVs are antithrombogenic and mechanically stable for 8 months in vivo. Histological analysis showed complete tissue integration and formation of vasa vasorum. The endothelium was confluent and positive for von Willebrand factor. A smooth muscle–specific α-actin–positive cell population developed within the TEBV, suggesting regeneration of a vascular media. Electron microscopy showed an endothelial basement membrane, elastogenesis and a complex collagen network. These results indicate that a completely biological and clinically relevant TEBV can be assembled exclusively from an individual's own cells.

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Figure 1: Short-term evaluation of TEBV in canine model.
Figure 2: Early remodeling of age- and risk-matched human TEBVs after implantation in athymic rats.
Figure 3: Late remodeling of age- and risk-matched human TEBVs after implantation in athymic rats.
Figure 4: Implantation of age- and risk-matched human TEBV in nonhuman primates.

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Acknowledgements

We thank Genzyme Transplant for providing antithymocyte globulin, Roche for providing mycophenolate mofetil (CellSept) and LifeNet for tissue-procurement assistance. We thank M. Haidekker for his help with the image processing of the computed tomography angiogram. This work was supported in part by a grant from the US National Institutes of Health Small Business Innovative Research (2R44HL64462 to N.L.). We thank M.L. Koranski for his help and for performing canine surgeries.

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Correspondence to Nicolas L'Heureux or Todd N McAllister.

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Todd N. McAllister is the Chief Executive Officer and Nicolas LHeureux is the Chief Scientific Officer of Cytograft Tissue Engineering. They also hold a significant portion of the stocks of Cytograft. Nathalie Dusserre and Gerhardt Koenig are employees of Cytograft. Robert C. Robbins has a small number of shares of Cytograft.

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L'Heureux, N., Dusserre, N., Konig, G. et al. Human tissue-engineered blood vessels for adult arterial revascularization. Nat Med 12, 361–365 (2006). https://doi.org/10.1038/nm1364

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