title: Engineering vascularized flaps using adipose-derived microvascular endothelial cells and mesenchymal stem cells.
abstract: Human adipose-derived microvascular endothelial cells (HAMEC) and mesenchymal stem cells (MSC) have been shown to bear angiogenic and vasculogenic capabilities. We hypothesize that co-culturing HAMEC:MSC on a porous biodegradable scaffold in vitro, later implanted as a graft around femoral blood vessels in a rat, will result in its vascularization by host vessels, creating a functional vascular flap that can effectively treat a range of large full-thickness soft tissue defects. HAMEC were co-cultured with MSC on polymeric three-dimensional porous constructs. Grafts were then implanted around the femoral vessels of a rat. To ensure vessel sprouting from the main femoral vessels, grafts were pre-isolated from the surrounding tissue. Graft vascularization was monitored to confirm full vascularization before flap transfer. Flaps were then transferred to treat both abdominal wall and exposed bone and tendon of an ankle defects. Flaps were analysed to determine vascular properties in terms of maturity, functionality and survival of implanted cells. Findings show that pre-isolated grafts bearing the HAMEC:MSC combination promoted formation of highly vascularized flaps, which were better integrated in both defect models. The results of this study show the essentiality of a specific adipose-derived cell combination in successful graft vascularization and integration, two processes crucial for flap survival. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Inter-departmental Program in Biotechnology, Technion - Israel Institute of Technology, Haifa, Israel.|Biomedical Engineering Department, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Freiman
authors.affiliation: Biomedical Engineering Department, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Yulia
authors.identifier: 0000-0002-6038-3109
authors.initials: Y
authors.lastname: Shandalov
authors.affiliation: Biomedical Engineering Department, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Dekel
authors.initials: D
authors.lastname: Rosenfeld
authors.affiliation: Biomedical Engineering Department, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Erez
authors.initials: E
authors.lastname: Shor
authors.affiliation: Bonus BioGroup Ltd, Haifa, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Ben-David
authors.affiliation: Bonus BioGroup Ltd, Haifa, Israel.
authors.forename: Shai
authors.initials: S
authors.lastname: Meretzki
authors.affiliation: Biomedical Engineering Department, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Shulamit
authors.initials: S
authors.lastname: Levenberg
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaplan Hospital, Rehovot, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Egozi
mesh_terms: D034861:Abdominal Wall / Q000098:blood supply; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001807:Blood Vessel Prosthesis; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D006801:Humans; D020007:Implants, Experimental; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D055806:Microvessels / Q000166:cytology*; D018919:Neovascularization, Physiologic; D017208:Rats, Wistar; D013524:Surgical Flaps / Q000098:blood supply; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
keywords: endothelial cells; flap; mesenchymal stem cells; regenerative medicine; tissue engineering; vascularization