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Pericyte modulation by a functional antibody obtained by a novel single cell selection strategy

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DOI

  • Jesper Just
  • Simon Lykkemark, Sino-Danish Centre for Education and Research (SDC)
  • ,
  • Charlotte Høgsbjerg Nielsen
  • ,
  • Ali Reza Roshenas, Department of Engineering, Aarhus University, Gustav Wieds Vej 10, 8000 Aarhus C, Aarhus, Denmark. pk@eng.au.dk.
  • ,
  • Kim Ryun Drasbek
  • Steen Vang Petersen
  • Toke Bek
  • Peter Kristensen

OBJECTIVE: 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.

METHODS: In order 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 towards relevant pericyte epitopes.

RESULTS: 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.

CONCLUSIONS: 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. This article is protected by copyright. All rights reserved.

OriginalsprogEngelsk
Artikelnummere12365
TidsskriftMicrocirculation
Vol/bind24
Nummer6
ISSN1073-9688
DOI
StatusUdgivet - aug. 2017

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