Capture of endothelial progenitor cells by a bispecific protein/monoclonal antibody molecule induces reendothelialization of vascular lesions

Harald F. Langer, Juergen W. von der Ruhr, Karin Daub, Tanja Schoenberger, Konstantinos Stellos, Andreas E. May, Hannah Schnell, Alexandra Gauss, Ramona Hafner, Peter Lang, Michael Schumm, Hans-Joerg Buehring, Karin Klingel, Sabine Conrad, Martin Schaller, Marc van Zandvoort, Gundram Jung, Stefanie Dimmeler, Thomas Skutella*, Meinrad Gawaz

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Web of Science)

Abstract

Tissue injury is inevitably accompanied by disruption of the endothelium and exposure of the subendothelial matrix. To generate a guidance molecule directing progenitor cells to sites of vascular lesions, we designed a bifunctional protein. The protein consists of the soluble platelet collagen receptor glycoprotein VI and an antibody to CD133 (hereafter called GPVI-CD133). In vitro and in vivo, this construct substantially mediates endothelial progenitor cell (EPC) homing to vascular lesions. Exposure of EPCs to GPVI-CD133 did not impair their capability to differentiate toward mature endothelial cells as verified by the formation of colony-forming units, the upregulation of endothelial markers CD31 and CD146 analyzed by flow cytometry or von Willebrand factor and endoglin assessed by immunofluorescence microscopy, as well as the presence of Weibel-Palade bodies using transmission electron microscopy. In vivo, GPVI-CD133 augments reendothelialization of vascular lesions. Thus, this bifunctional protein could be a potential new therapeutic option for cardiovascular diseases.
Original languageEnglish
Pages (from-to)687-699
JournalJournal of Molecular Medicine
Volume88
Issue number7
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Regenerative medicine
  • Endothelialization
  • Progenitor cells
  • Stem cells
  • Vascular injury
  • Guidance molecule
  • Vascular disease
  • Therapy

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