Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling.
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.
Roh
Jason D
JD
Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06510, USA. jdroh79@gmail.com
Sawh-Martinez
Rajendra
R
Brennan
Matthew P
MP
Jay
Steven M
SM
Devine
Lesley
L
Rao
Deepak A
DA
Yi
Tai
T
Mirensky
Tamar L
TL
Nalbandian
Ani
A
Udelsman
Brooks
B
Hibino
Narutoshi
N
Shinoka
Toshiharu
T
Saltzman
W Mark
WM
Snyder
Edward
E
Kyriakides
Themis R
TR
Pober
Jordan S
JS
Breuer
Christopher K
CK
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
D018932:Chemokine CCL2; D019408:Platelet Endothelial Cell Adhesion Molecule-1