Regenerative Medicine

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Integration of Blood Outgrowth Endothelial Cells in Dermal Fibroblast Sheets Promotes Full Thickness Wound Healing†‡§

  1. Benoit Hendrickx1,2,
  2. Kristoff Verdonck1,2,
  3. Stefaan Van den Berge2,
  4. Stijn Dickens2,
  5. Elof Eriksson3,
  6. Jan Jeroen Vranckx2,
  7. Aernout Luttun1,¶,*

Article first published online: 18 MAY 2010

DOI: 10.1002/stem.445

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 7, pages 1165–1177, July 2010

Additional Information

How to Cite

Hendrickx, B., Verdonck, K., Van den Berge, S., Dickens, S., Eriksson, E., Vranckx, J. J. and Luttun, A. (2010), Integration of Blood Outgrowth Endothelial Cells in Dermal Fibroblast Sheets Promotes Full Thickness Wound Healing. STEM CELLS, 28: 1165–1177. doi: 10.1002/stem.445

Author Information

  1. 1

    Center for Molecular and Vascular Biology, KULeuven, Leuven, Belgium

  2. 2

    Department of Plastic, Reconstructive and Aesthetic Surgery, KULeuven, Leuven, Belgium

  3. 3

    Laboratory of Tissue Repair and Gene Transfer, Harvard Medical School, Division of Plastic Surgery, Brigham and Woman's Hospital, Boston, USA

  1. Telephone: +3216345772; Fax: +3216345990

*Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs & Navorsing 1, Herestraat 49, B-3000 Leuven, Belgium

  1. †

    Author contributions: B.H.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; K.V. and S.VdB.: conception and design, provision of study material, manuscript writing; S.D.: collection and assembly of data, data analysis and interpretation; E.E.: manuscript writing; J.J.V.: manuscript writing, final approval of the manuscript; A.L.: conception and design, data analysis and interpretation, manuscript writing, final approval of the manuscript.

  2. ‡

    First published online in STEM CELLSEXPRESS May 18, 2010.

  3. §

    Disclosure of potential conflicts of interest is found at the end of this article.

Publication History

  1. Issue published online: 20 JUL 2010
  2. Article first published online: 18 MAY 2010
  3. Manuscript Accepted: 10 MAY 2010
  4. Manuscript Received: 9 DEC 2009

Funded by

  • European Commission. Grant Number: FP7-StG-IMAGINED 203291
  • FWO
  • KULeuven Center of Excellence Grant. Grant Number: EF/05/013

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Keywords:

  • Endothelial cells;
  • Angiogenesis;
  • Autologous stem cell transplantation;
  • Hypoxia;
  • Peripheral blood stem cells;
  • Progenitor cells;
  • Tissue regeneration;
  • Skin grafts

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

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