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

Alina Freiman, Yulia Shandalov, Dekel Rosenfeld, Erez Shor, Dror Ben-David, Shai Meretzki, Shulamit Levenberg*, Dana Egozi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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.

Original languageEnglish
Pages (from-to)e130-e141
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume12
Issue number1
DOIs
StatePublished - Jan 2018
Externally publishedYes

Funding

FundersFunder number
European Research Council281501
Seventh Framework ProgrammeFP/2007‐2013
Horizon 202050654, 640579

    Keywords

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

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