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 language | English (US) |
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Article number | e0255075 |
Pages (from-to) | e0255075 |
Journal | PLoS ONE |
Volume | 16 |
Issue number | 8 |
DOIs | |
State | Published - 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