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J Tissue Eng Regen Med. 2018 Jan;12(1):e130-e141. doi: 10.1002/term.2436. Epub 2017 Jun 23.

Engineering vascularized flaps using adipose-derived microvascular endothelial cells and mesenchymal stem cells.

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Inter-departmental Program in Biotechnology, Technion - Israel Institute of Technology, Haifa, Israel.
Biomedical Engineering Department, Technion - Israel Institute of Technology, Haifa, Israel.
Bonus BioGroup Ltd, Haifa, Israel.
Department of Plastic and Reconstructive Surgery, Kaplan Hospital, Rehovot, Israel.


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.


endothelial cells; flap; mesenchymal stem cells; regenerative medicine; tissue engineering; vascularization


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