Induced endothelial cells from peripheral arterial disease patients and neonatal fibroblasts have comparable angiogenic properties

Jack D. Hywood, Sara Sadeghipour, Zoe E. Clayton, Jun Yuan, Colleen Stubbs, Jack W.T. Wong, John P. Cooke, Sanjay Patel

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Induced endothelial cells (iECs) generated from neonatal fibroblasts via transdifferentiation have been shown to have pro-angiogenic properties and are a potential therapy for peripheral arterial disease (PAD). It is unknown if iECs can be generated from fibroblasts collected from PAD patients and whether these cells are pro-angiogenic. In this study fibroblasts were collected from four PAD patients undergoing carotid endarterectomies. These cells, and neonatal fibroblasts, were transdifferentiated into iECs using modified mRNA. Endothelial phenotype and pro-angiogenic cytokine secretion were investigated. NOD-SCID mice underwent surgery to induce hindlimb ischaemia in a murine model of PAD. Mice received intramuscular injections with either control vehicle, or 1 × 106 neonatal-derived or 1 × 106 patient-derived iECs. Recovery in perfusion to the affected limb was measured using laser Doppler scanning. Perfusion recovery was enhanced in mice treated with neonatal-derived iECs and in two of the three patient-derived iEC lines investigated in vivo. Patient-derived iECs can be successfully generated from PAD patients and for specific patients display comparable pro-angiogenic properties to neonatal-derived iECs.

Original languageEnglish (US)
Article numbere0255075
Pages (from-to)e0255075
JournalPLoS ONE
Volume16
Issue number8
DOIs
StatePublished - Aug 2021

Keywords

  • Acetylation/drug effects
  • Animals
  • Capillaries/drug effects
  • Cell Line
  • Cell Movement/drug effects
  • Cell Transdifferentiation/drug effects
  • Collagen/pharmacology
  • Culture Media, Conditioned/pharmacology
  • Cytokines/metabolism
  • Drug Combinations
  • Endothelial Cells/drug effects
  • Fibroblasts/drug effects
  • Hindlimb/blood supply
  • Humans
  • Infant, Newborn
  • Intercellular Signaling Peptides and Proteins/pharmacology
  • Ischemia/pathology
  • Laminin/pharmacology
  • Lipoproteins, LDL/metabolism
  • Male
  • Mice, Inbred NOD
  • Mice, SCID
  • Neovascularization, Physiologic/drug effects
  • Perfusion
  • Peripheral Arterial Disease/pathology
  • Plant Lectins/metabolism
  • Protein Binding/drug effects
  • Proteoglycans/pharmacology

ASJC Scopus subject areas

  • General

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