title: Decellularized tissue-engineered blood vessel as an arterial conduit.
abstract: Arterial tissue-engineering techniques that have been reported previously typically involve long waiting times of several months while cells from the recipient are cultured to create the engineered vessel. In this study, we developed a different approach to arterial tissue engineering that can substantially reduce the waiting time for a graft. Tissue-engineered vessels (TEVs) were grown from banked porcine smooth muscle cells that were allogeneic to the intended recipient, using a biomimetic perfusion system. The engineered vessels were then decellularized, leaving behind the mechanically robust extracellular matrix of the graft wall. The acellular grafts were then seeded with cells that were derived from the intended recipient--either endothelial progenitor cells (EPC) or endothelial cell (EC)--on the graft lumen. TEV were then implanted as end-to-side grafts in the porcine carotid artery, which is a rigorous testbed due to its tendency for graft occlusion. The EPC- and EC-seeded TEV all remained patent for 30 d in this study, whereas the contralateral control vein grafts were patent in only 3/8 implants. Going along with the improved patency, the cell-seeded TEV demonstrated less neointimal hyperplasia and fewer proliferating cells than did the vein grafts. Proteins in the mammalian target of rapamycin signaling pathway tended to be decreased in TEV compared with vein grafts, implicating this pathway in the TEV's resistance to occlusion from intimal hyperplasia. These results indicate that a readily available, decellularized tissue-engineered vessel can be seeded with autologous endothelial progenitor cells to provide a biological vascular graft that resists both clotting and intimal hyperplasia. In addition, these results show that engineered connective tissues can be grown from banked cells, rendered acellular, and then used for tissue regeneration in vivo.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
authors.forename: Clay
authors.initials: C
authors.lastname: Quint
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kondo
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Manson
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lawson
authors.forename: Alan
authors.initials: A
authors.lastname: Dardik
authors.forename: Laura E
authors.initials: LE
authors.lastname: Niklason
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology*; D001777:Blood Coagulation; D001807:Blood Vessel Prosthesis; D002339:Carotid Arteries / Q000473:pathology; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D010477:Perfusion; D044968:Regenerative Medicine / Q000379:methods*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D020123:Sirolimus