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

• Published in: PloS one Vol. 16; no. 8
• Main Authors: Jack D. Hywood, Sara Sadeghipour, Zoe E. Clayton, Jun Yuan, Colleen Stubbs, Jack W. T. Wong, John P. Cooke, Sanjay Patel
• Format: Journal Article
• Language: English
• Published: Public Library of Science (PLoS) 01.01.2021
• ISSN: 1932-6203

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.