title: Evidence for in vivo growth potential and vascular remodeling of tissue-engineered artery.
abstract: Nondegradable synthetic polymer vascular grafts currently used in cardiovascular surgery have no growth potential. Tissue-engineered vascular grafts (TEVGs) may solve this problem. In this study, we developed a TEVG using autologous bone marrow-derived cells (BMCs) and decellularized tissue matrices, and tested whether the TEVGs exhibit growth potential and vascular remodeling in vivo. Vascular smooth muscle-like cells and endothelial-like cells were differentiated from bone marrow mononuclear cells in vitro. TEVGs were fabricated by seeding these cells onto decellularized porcine abdominal aortas and implanted into the abdominal aortas of 4-month-old, bone marrow donor pigs (n = 4). Eighteen weeks after implantation, the dimensions of TEVGs were measured and compared with those of native abdominal aortas. Expression of molecules associated with vascular remodeling was examined with reverse transcription-polymerase chain reaction assay and immunohistochemistry. Eighteen weeks after implantation, all TEVGs were patent with no sign of thrombus formation, dilatation, or stenosis. Histological and immunohistochemical analyses of the retrieved TEVGs revealed regeneration of endothelium and smooth muscle and the presence of collagen and elastin. The outer diameter of three of the four TEVGs increased in proportion to increases in body weight and outer native aorta diameter. Considerable extents of expression of molecules associated with extracellular matrix (ECM) degradation (i.e., matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase) and ECM precursors (i.e., procollagen I, procollagen III, and tropoelastin) occurred in the TEVGs, indicating vascular remodeling associated with degradation of exogenous ECMs (implanted decellularized matrices) and synthesis of autologous ECMs. This study demonstrates that the TEVGs with autologous BMCs and decellularized tissue matrices exhibit growth potential and vascular remodeling in vivo of tissue-engineered artery.
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul, Korea.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Il-Kwon
authors.initials: IK
authors.lastname: Kim
authors.forename: Jin Muk
authors.initials: JM
authors.lastname: Kang
authors.forename: Kang Won
authors.initials: KW
authors.lastname: Song
authors.forename: Hong Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Chang Hwan
authors.initials: CH
authors.lastname: Park
authors.forename: Kyung Jong
authors.initials: KJ
authors.lastname: Yoo
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001807:Blood Vessel Prosthesis; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D014333:Tropoelastin / Q000378:metabolism
chemical_list: D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014333:Tropoelastin