Title: Integration of Blood Outgrowth Endothelial Cells in Dermal Fibroblast Sheets Promotes Full Thickness Wound Healing
Authors: Hendrickx, Benoit
Verdonck, Kristoff
Van den Berge, Stefaan
Dickens, Stijn
Eriksson, Elof
Vranckx, Jan
Luttun, Aernout # ×
Issue Date: Jul-2010
Publisher: AlphaMed Press
Series Title: Stem Cells vol:28 issue:7 pages:1165-1177
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. STEM CELLS 2010;28:1165-1177
ISSN: 1066-5099
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Plastic, Reconstructive and Estetic Surgery Section (-)
× corresponding author
# (joint) last author

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