title: Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling.
abstract: Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds. As in humans, TEVGs implanted in a mouse host as venous interposition grafts gradually transformed into living blood vessels over a 6-month time course. Seeded hBMCs, however, were no longer detectable within a few days of implantation. Instead, scaffolds were initially repopulated by mouse monocytes and subsequently repopulated by mouse SMCs and ECs. Seeded BMCs secreted significant amounts of monocyte chemoattractant protein-1 and increased early monocyte recruitment. These findings suggest TEVGs transform into functional neovessels via an inflammatory process of vascular remodeling.
authors.affiliation: Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06510, USA. jdroh79@gmail.com
authors.forename: Jason D
authors.initials: JD
authors.lastname: Roh
authors.forename: Rajendra
authors.initials: R
authors.lastname: Sawh-Martinez
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Brennan
authors.forename: Steven M
authors.initials: SM
authors.lastname: Jay
authors.forename: Lesley
authors.initials: L
authors.lastname: Devine
authors.forename: Deepak A
authors.initials: DA
authors.lastname: Rao
authors.forename: Tai
authors.initials: T
authors.lastname: Yi
authors.forename: Tamar L
authors.initials: TL
authors.lastname: Mirensky
authors.forename: Ani
authors.initials: A
authors.lastname: Nalbandian
authors.forename: Brooks
authors.initials: B
authors.lastname: Udelsman
authors.forename: Narutoshi
authors.initials: N
authors.lastname: Hibino
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shinoka
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
authors.forename: Edward
authors.initials: E
authors.lastname: Snyder
authors.forename: Themis R
authors.initials: TR
authors.lastname: Kyriakides
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Pober
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Breuer
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000379:methods*; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D016513:Mice, SCID; D008855:Microscopy, Electron, Scanning; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014183:Transplantation, Heterologous
chemical_list: D018932:Chemokine CCL2; D019408:Platelet Endothelial Cell Adhesion Molecule-1