Open AccessInduced endothelial cells from peripheral arterial disease patients and neonatal fibroblasts have comparable angiogenic properties
Author(s) -
Jack D. Hywood,
Sara Sadeghipour,
Zoe Clayton,
Jun Yuan,
Colleen Stubbs,
Wing Tak Wong,
John P. Cooke,
Sanjay Patel
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0255075
Subject(s) - medicine , transdifferentiation , perfusion , angiogenesis , in vivo , pathology , in vitro , biology , biochemistry , microbiology and biotechnology
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 × 10 6 neonatal-derived or 1 × 10 6 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.