title: Pericyte modulation by a functional antibody obtained by a novel single-cell selection strategy.
abstract: Pericytes surround the endothelial cells of the microvasculature where they serve as active participants in crucial vascular functions such as angiogenesis, stability, and permeability. However, pericyte loss or dysfunction has been described in a number of pathologies. Targeting pericytes could therefore prove instrumental in the further development of vascular therapeutics.
  
  
  
  To target the pericyte, a proteomic-based approach using antibody phage display was conducted. We present a novel single-cell selection strategy, with a modified selection step to drive the selection of antibodies toward relevant pericyte epitopes.
  
  
  
  Characterization of the selected antibodies revealed two antibodies with binding specificity for pericytes. The cognate antigen of one of the antibodies was identified as pericyte-expressed fibronectin. This antibody was shown to be a potent inhibitor of pericyte migration and to induce a pro-angiogenic response when included in a pericyte-endothelial cell co-culture angiogenesis assay.
  
  
  
  The selection method provides an efficient platform for the selection of functional antibodies which target pericytes. We obtain an antibody that interacts with a fibronectin epitope important for pericyte mobility and functionality. Targeting of this epitope in pathologies where pericytes are implicated could potentially be of therapeutic benefit.
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.|Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Just
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.|Sino-Danish Centre for Education and Research (SDC), Aarhus C, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Lykkemark
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Nielsen
authors.affiliation: Department of Engineering, Aarhus University, Aarhus C, Denmark.
authors.forename: Ali R
authors.initials: AR
authors.lastname: Roshenas
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.
authors.forename: Kim R
authors.initials: KR
authors.lastname: Drasbek
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
authors.forename: Steen V
authors.initials: SV
authors.lastname: Petersen
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.
authors.forename: Toke
authors.initials: T
authors.lastname: Bek
authors.affiliation: Department of Engineering, Aarhus University, Aarhus C, Denmark.
authors.forename: Peter
authors.identifier: 0000-0001-7205-6853
authors.initials: P
authors.lastname: Kristensen
mesh_terms: D000906:Antibodies / Q000494:pharmacology* / Q000627:therapeutic use; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D005353:Fibronectins / Q000276:immunology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020286:Pericytes / Q000187:drug effects*; D040901:Proteomics / Q000379:methods*; D059010:Single-Cell Analysis
chemical_list: D000906:Antibodies; D005353:Fibronectins
keywords: angiogenesis; fibronectin; pericyte; phage display; recombinant antibodies