Human tissue-engineered blood vessels for adult arterial revascularization

Nicolas L'Heureux¹, Nathalie Dusserre¹, Gerhardt Konig¹, Braden Victor², Paul Keire³, Thomas N Wight³, Nicolas A F Chronos⁴, Andrew E Kyles⁵, Clare R Gregory⁵, Grant Hoyt⁶, Robert C Robbins⁶ & Todd N McAllister¹

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

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

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

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

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

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

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 -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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