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

Jesper Just, Simon Lykkemark, Charlotte H. Nielsen, Ali R. Roshenas, Kim R. Drasbek, Steen V. Petersen, Toke Bek, Peter Kristensen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

3 Citations (Scopus)

Abstract

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: 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. 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.

Original languageEnglish
Article numbere12365
JournalMicrocirculation
Volume24
Issue number6
ISSN1073-9688
DOIs
Publication statusPublished - 1 Aug 2017
Externally publishedYes

Keywords

  • angiogenesis
  • fibronectin
  • pericyte
  • phage display
  • recombinant antibodies

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