title: Integration of blood outgrowth endothelial cells in dermal fibroblast sheets promotes full thickness wound healing.
abstract: Vascularization is the cornerstone of wound healing. We introduced human blood outgrowth endothelial cells (hBOEC) in a self-assembled human dermal fibroblast sheet (hDFS), intended as a tissue-engineered dermal substitute with inherent vascular potential. hBOEC were functionally and molecularly different from early endothelial progenitor cells and human umbilical vein endothelial cells (HUVEC). hBOEC alone, unlike HUVEC, efficiently revascularized and re-oxygenated the wound bed, both by active incorporation into new vessels and by trophic stimulation of host angiogenesis in a dose-dependent manner. Furthermore, hBOEC alone, but not HUVEC, accelerated epithelial coverage and matrix organization of the wound bed. In addition, integration of hBOEC in hDFS not only further improved vascularization, epithelial coverage and matrix organization but also prevented excessive wound contraction. In vitro analyses with hBOEC, fibroblasts and keratinocytes revealed that these effects were both due to growth factor crosstalk and to short cutting hypoxia. Among multiple growth factors secreted by hBOEC, placental growth factor mediated at least in part the beneficial effects on keratinocyte migration and proliferation. Overall, this combined tissue engineering approach paves the way for clinical development of a fully autologous vascularized dermal substitute for patients with large skin defects that do not heal properly.
authors.affiliation: Center for Molecular and Vascular Biology, KULeuven, Leuven, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Hendrickx
authors.forename: Kristoff
authors.initials: K
authors.lastname: Verdonck
authors.forename: Stefaan
authors.initials: S
authors.lastname: Van den Berge
authors.forename: Stijn
authors.initials: S
authors.lastname: Dickens
authors.forename: Elof
authors.initials: E
authors.lastname: Eriksson
authors.forename: Jan Jeroen
authors.initials: JJ
authors.lastname: Vranckx
authors.forename: Aernout
authors.initials: A
authors.lastname: Luttun
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D018919:Neovascularization, Physiologic; D010100:Oxygen / Q000378:metabolism; D014945:Wound Healing
chemical_list: D010100:Oxygen