The recombinant bifunctional protein αCD133-GPVI promotes repair of the infarcted myocardium in mice

J Thromb Haemost. 2012 Jun;10(6):1152-64. doi: 10.1111/j.1538-7836.2012.04710.x.

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.

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / immunology*
  • Binding Sites
  • Cell Adhesion
  • Cell Differentiation
  • Disease Models, Animal
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Endothelial Cells / transplantation*
  • Extracellular Matrix Proteins / metabolism
  • Genetic Therapy*
  • Glycoproteins / immunology*
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Myocardial Infarction / genetics
  • Myocardial Infarction / immunology
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Myocardium / immunology
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Peptides / immunology*
  • Platelet Membrane Glycoproteins / biosynthesis*
  • Platelet Membrane Glycoproteins / genetics
  • Recombinant Proteins / biosynthesis
  • Regeneration*
  • Single-Chain Antibodies / biosynthesis*
  • Single-Chain Antibodies / genetics
  • Stem Cell Transplantation*
  • Time Factors
  • Transfection
  • Ventricular Function, Left

Substances

  • AC133 Antigen
  • Antigens, CD
  • Extracellular Matrix Proteins
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Platelet Membrane Glycoproteins
  • Prom1 protein, mouse
  • Recombinant Proteins
  • Single-Chain Antibodies
  • platelet membrane glycoprotein VI