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Human tissue-engineered blood vessels for adult arterial revascularization

Nature Medicine volume 12, pages 361–365 (2006)Cite this article

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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References

  1. Weinberg, C.B. & Bell, E. A blood vessel model constructed from collagen and cultured vascular cells. Science 231, 397–400 (1986).

    Article  CAS  Google Scholar 

  2. Niklason, L.E. et al. Functional arteries grown in vitro. Science 284, 489–493 (1999).

    Article  CAS  Google Scholar 

  3. Chue, W.L. et al. Dog peritoneal and pleural cavities as bioreactors to grow autologous vascular grafts. J. Vasc. Surg. 39, 859–867 (2004).

    Article  Google Scholar 

  4. Kakisis, J.D., Liapis, C.D., Breuer, C. & Sumpio, B.E. Artificial blood vessel: the Holy Grail of peripheral vascular surgery. J. Vasc. Surg. 41, 349–354 (2005).

    Article  Google Scholar 

  5. L'Heureux, N., Germain, L., Labbe, R. & Auger, F.A. In vitro construction of a human blood vessel from cultured vascular cells: a morphologic study. J. Vasc. Surg. 17, 499–509 (1993).

    Article  CAS  Google Scholar 

  6. L'Heureux, N., Paquet, S., Labbe, R., Germain, L. & Auger, F.A. A completely biological tissue-engineered human blood vessel. FASEB J. 12, 47–56 (1998).

    Article  CAS  Google Scholar 

  7. McKee, J.A. et al. Human arteries engineered in vitro. EMBO Rep. 4, 633–638 (2003).

    Article  CAS  Google Scholar 

  8. Poh, M. et al. Blood vessels engineered from human cells. Lancet 365, 2122–2124 (2005).

    Article  Google Scholar 

  9. Shin'oka, T., Imai, Y. & Ikada, Y. Transplantation of a tissue-engineered pulmonary artery. N. Engl. J. Med. 344, 532–533 (2001).

    Article  CAS  Google Scholar 

  10. Niklason, L.E. Replacement arteries made to order. Science 286, 1493–1494 (1999).

    Article  CAS  Google Scholar 

  11. L'Heureux, N. et al. A human tissue-engineered vascular media: a new model for pharmacological studies of contractile responses. FASEB J. 15, 515–524 (2001).

    Article  CAS  Google Scholar 

  12. Michel, M. et al. Characterization of a new tissue-engineered human skin equivalent with hair. In Vitro Cell. Dev. Biol. Anim. 35, 318–326 (1999).

    Article  CAS  Google Scholar 

  13. Berglund, J.D., Mohseni, M.M., Nerem, R.M. & Sambanis, A. A biological hybrid model for collagen-based tissue engineered vascular constructs. Biomaterials 24, 1241–1254 (2003).

    Article  CAS  Google Scholar 

  14. Grenier, G. et al. Isolation and culture of the three vascular cell types from a small vein biopsy sample. In Vitro Cell. Dev. Biol. Anim. 39, 131–139 (2003).

    Article  Google Scholar 

  15. Davis, C., Fischer, J., Ley, K. & Sarembock, I.J. The role of inflammation in vascular injury and repair. J. Thromb. Haemost. 1, 1699–1709 (2003).

    Article  CAS  Google Scholar 

  16. Gittenberger-de Groot, A.C., DeRuiter, M.C., Bergwerff, M. & Poelmann, R.E. Smooth muscle cell origin and its relation to heterogeneity in development and disease. Arterioscler. Thromb. Vasc. Biol. 19, 1589–1594 (1999).

    Article  CAS  Google Scholar 

  17. Wight, T.N. The vascular extracellular matrix. in Artherosclerosis and Coronary Artery Disease (eds. Fuster, V., Ross, R. & Topol, E.) 421–440 (Raven Press, New York, 1996).

    Google Scholar 

  18. Lamm, P., Juchem, G., Milz, S., Schuffenhauer, M. & Reichart, B. Autologous endothelialized vein allograft: a solution in the search for small-caliber grafts in coronary artery bypass graft operations. Circulation 104, I108–I114 (2001).

    Article  CAS  Google Scholar 

  19. Dobrin, P.B. Mechanical behavior of vascular smooth muscle in cylindrical segments of arteries in vitro. Ann. Biomed. Eng. 12, 497–510 (1984).

    Article  CAS  Google Scholar 

  20. Cambria, R.P. et al. The evolution of morphologic and biomechanical changes in reversed and in-situ vein grafts. Ann. Surg. 205, 167–174 (1987).

    Article  CAS  Google Scholar 

  21. van der Lugt, A. et al. Femorodistal venous bypass evaluated with intravascular ultrasound. Eur. J. Vasc. Endovasc. Surg. 9, 394–402 (1995).

    Article  CAS  Google Scholar 

  22. Varty, K., Porter, K., Bell, P.R. & London, N.J. Vein morphology and bypass graft stenosis. Br. J. Surg. 83, 1375–1379 (1996).

    Article  CAS  Google Scholar 

  23. Chamiot-Clerc, P., Copie, X., Renaud, J.F., Safar, M. & Girerd, X. Comparative reactivity and mechanical properties of human isolated internal mammary and radial arteries. Cardiovasc. Res. 37, 811–819 (1998).

    Article  CAS  Google Scholar 

  24. Girerd, X.J. et al. Incompressibility of the human arterial wall: an in vitro ultrasound study. J. Hypertens. Suppl. 10, S111–S114 (1992).

    CAS  PubMed  Google Scholar 

  25. van Son, J.A., Smedts, F., Vincent, J.G., van Lier, H.J. & Kubat, K. Comparative anatomic studies of various arterial conduits for myocardial revascularization. J. Thorac. Cardiovasc. Surg. 99, 703–707 (1990).

    CAS  PubMed  Google Scholar 

  26. van Andel, C.J., Pistecky, P.V. & Borst, C. Mechanical properties of porcine and human arteries: implications for coronary anastomotic connectors. Ann. Thorac. Surg. 76, 58–65 (2003).

    Article  Google Scholar 

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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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Authors and Affiliations

  1. Cytograft Tissue Engineering, Inc., 3 Hamilton Landing, Suite 220, Novato, 94949, California, USA

    Nicolas L'Heureux, Nathalie Dusserre, Gerhardt Konig & Todd N McAllister

  2. Capitol Cardiovascular Imaging Center, 1315 Alhambra Boulevard, Suite 320, Sacramento, 95816, California, USA

    Braden Victor

  3. The Hope Heart Program, Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, 98101, Washington, USA

    Paul Keire & Thomas N Wight

  4. American Cardiovascular Research Institute, 5665 Peachtree Dunwoody Road, Suite 225, Outpatient Center, Atlanta, 30342, Georgia, USA

    Nicolas A F Chronos

  5. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, 95616, California, USA

    Andrew E Kyles & Clare R Gregory

  6. Department of Cardiothoracic Surgery, Falk Cardiovascular Research Center, Stanford University, 300 Pasteur Drive, Stanford, 94305, California, USA

    Grant Hoyt & Robert C Robbins

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  1. Nicolas L'Heureux
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  9. Clare R Gregory
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  12. Todd N McAllister
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Corresponding authors

Correspondence to Nicolas L'Heureux or Todd N McAllister.

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Competing interests

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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