title: The recombinant bifunctional protein αCD133-GPVI promotes repair of the infarcted myocardium in mice.
abstract: BACKGROUND
  Bone-marrow-derived progenitor cells are important in myocardial repair mechanisms following prolonged ischemia. Cell-based therapy of diseased myocardium is limited by a low level of tissue engraftment.
  
  
  OBJECTIVE
  The aim of this study was the development of the bifunctional protein αCD133-glycoprotein (GP)VI as an effective treatment for supporting vascular and myocardial repair mechanisms.
  
  
  RESULTS
  We have generated and characterized a bifunctional molecule (αCD133-GPVI) that binds both to the subendothelium of the injured microvasculature and to CD133(+) progenitor cells with high affinity. αCD133-GPVI enhances progenitor cell adhesion to extracellular matrix proteins and differentiation into mature endothelial cells. In vivo studies showed that αCD133-GPVI favors adhesion of circulating progenitor cells to the injured vessel wall (intravital microscopy). Also, treatment of mice undergoing experimental myocardial infarction with αCD133-GPVI-labeled progenitor cells reduces infarction size and preserves myocardial function.
  
  
  CONCLUSIONS
  The bifunctional trapping protein αCD133-GPVI represents a novel and promising therapeutic option for limiting heart failure of the ischemic myocardium.
authors.affiliation: NMI, Natural and Medical Sciences Institute at the University of Tübingen, Regenerative Medicine I, Reutlingen University Clinic of Tübingen, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Baumer
authors.forename: C
authors.initials: C
authors.lastname: Leder
authors.forename: M
authors.initials: M
authors.lastname: Ziegler
authors.forename: T
authors.initials: T
authors.lastname: Schönberger
authors.forename: C
authors.initials: C
authors.lastname: Ochmann
authors.forename: A
authors.initials: A
authors.lastname: Perk
authors.forename: H
authors.initials: H
authors.lastname: Degen
authors.forename: B
authors.initials: B
authors.lastname: Schmid-Horch
authors.forename: M
authors.initials: M
authors.lastname: Elvers
authors.forename: G
authors.initials: G
authors.lastname: Münch
authors.forename: M
authors.initials: M
authors.lastname: Ungerer
authors.forename: B
authors.initials: B
authors.lastname: Schlosshauer
authors.forename: M
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001665:Binding Sites; D002448:Cell Adhesion; D002454:Cell Differentiation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D015316:Genetic Therapy; D006023:Glycoproteins / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000276:immunology*; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D012038:Regeneration; D057127:Single-Chain Antibodies / Q000096:biosynthesis* / Q000235:genetics; D033581:Stem Cell Transplantation; D013997:Time Factors; D014162:Transfection; D016277:Ventricular Function, Left
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D010980:Platelet Membrane Glycoproteins; C000606024:Prom1 protein, mouse; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies; C098341:platelet membrane glycoprotein VI