Capture of endothelial progenitor cells by a bispecific protein/monoclonal antibody molecule induces reendothelialization of vascular lesions.
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.
Langer
Harald F
HF
Medical Clini III, Department of Cardiovascular Medicine, Eberhard Karls University of Tübingen, Tübingen, Germany.
von der Ruhr
Jürgen W
JW
Daub
Karin
K
Schoenberger
Tanja
T
Stellos
Konstantinos
K
May
Andreas E
AE
Schnell
Hannah
H
Gauss
Alexandra
A
Hafner
Ramona
R
Lang
Peter
P
Schumm
Michael
M
Bühring
Hans-Jörg
HJ
Klingel
Karin
K
Conrad
Sabine
S
Schaller
Martin
M
van Zandvoort
Marc
M
Jung
Gundram
G
Dimmeler
Stefanie
S
Skutella
Thomas
T
Gawaz
Meinrad
M
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*
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