Vascular smooth muscle enhances functionality of tissue-engineered blood vessels in vivo

• Published in: Journal of vascular surgery Vol. 53; no. 2; pp. 426 - 434
• Main Authors: Neff, Lucas P., MD, Tillman, Bryan W., MD, PhD, Yazdani, Saami K., PhD, Machingal, Masood A., MS, Yoo, James J., MD, PhD, Soker, Shay, PhD, Bernish, Brian W., BS, Geary, Randolph L., MD, Christ, George J., PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-02-2011; Elsevier
• Subjects: Actins - metabolism; Animals; Biological and medical sciences; Bioprosthesis; Bioreactors; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation - instrumentation; Carotid Artery, Common - surgery; Cells, Cultured; Coculture Techniques; Endothelial Cells - transplantation; Female; Femoral Artery - surgery; Hormones. Endocrine system; Medical sciences; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - transplantation; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - transplantation; Myosin Heavy Chains - metabolism; Pharmacology. Drug treatments; Prosthesis Design; Pulsatile Flow; Sheep; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Time Factors; Tissue Engineering; Tissue Scaffolds; Transplantation, Homologous; Vascular Patency; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; Smooth muscle; Cardiovascular disease; Surgery
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/j.jvs.2010.07.054

Objectives There is significant room for improvement in the development of tissue-engineered blood vessels (TEBVs) for vascular reconstruction. Most commonly, TEBVs are seeded with endothelial cells (ECs) only. This provides an antithrombogenic surface but suboptimal physiologic characteristics compared with native arteries, due to lack of smooth muscle cells (SMCs) in the vessel media. Although SMCs are critical in vessel architecture and function throughout the vascular tree, few studies have incorporated SMCs in TEBVs implanted in vivo. As such, the goal of the present study was to evaluate the effect of SMC coseeding with ECs on TEBV maturation, structure, and function after prolonged in vivo maturation. Methods Dual-seeded TEBVs (dsTEBVs) were created by coseeding autologous ECs derived from circulating progenitor cells and SMCs from artery explants onto the lumen and outer surface of extracellular matrix scaffolds, respectively. Control vessels were seeded with ECs alone (ecTEBV). All vessels were preconditioned to pulsatile flow for 10 to 14 days in a bioreactor, implanted as arterial interposition grafts in sheep, and allowed to heal and adapt in vivo for 4 months before ex vivo physiologic testing and histologic analysis. Results All implants were patent at 4 months. There were no structural failures, aneurysms, or infectious complications. The dsTEBVs exhibited a greater degree of wall maturation, characterized by higher medial cellularity ( P = .01) and greater percentage of α-actin ( P = .005) and SMC-specific muscle myosin heavy chain ( P = .005) staining compared with ecTEBVs. Contractile responses to phenylephrine and serotonin were significantly greater in isolated rings of dsTEBVs than those observed in ecTEBVs ( P = .01). Conclusions To our knowledge, this is the first study that demonstrates enhanced in vivo wall maturation and contractile function of TEBVs coseeded with autologous SMCs and ECs compared with EC seeding alone. These data suggest a coseeding strategy can be accomplished in a clinically relevant timeframe (typically 6 weeks) and may provide advantages for arterial reconstruction compared with vessels engineered only with endothelium.