title: Capture of endothelial progenitor cells by a bispecific protein/monoclonal antibody molecule induces reendothelialization of vascular lesions.
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.
authors.affiliation: Medical Clini III, Department of Cardiovascular Medicine, Eberhard Karls University of Tübingen, Tübingen, Germany.
authors.forename: Harald F
authors.initials: HF
authors.lastname: Langer
authors.forename: Jürgen W
authors.initials: JW
authors.lastname: von der Ruhr
authors.forename: Karin
authors.initials: K
authors.lastname: Daub
authors.forename: Tanja
authors.initials: T
authors.lastname: Schoenberger
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stellos
authors.forename: Andreas E
authors.initials: AE
authors.lastname: May
authors.forename: Hannah
authors.initials: H
authors.lastname: Schnell
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gauss
authors.forename: Ramona
authors.initials: R
authors.lastname: Hafner
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: Michael
authors.initials: M
authors.lastname: Schumm
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Bühring
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.forename: Sabine
authors.initials: S
authors.lastname: Conrad
authors.forename: Martin
authors.initials: M
authors.lastname: Schaller
authors.forename: Marc
authors.initials: M
authors.lastname: van Zandvoort
authors.forename: Gundram
authors.initials: G
authors.lastname: Jung
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Thomas
authors.initials: T
authors.lastname: Skutella
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000473:pathology* / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D010980:Platelet Membrane Glycoproteins; C000606024:Prom1 protein, mouse; D011993:Recombinant Fusion Proteins; C098341:platelet membrane glycoprotein VI