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Robust revascularisation in multiple models of limb ischemia using a clinically translatable human stem cell-derived endothelial cell product

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http://linkinghub.elsevier.com/retrieve/pii/S1525001618301448
Original languageEnglish
JournalMolecular Therapy
Volume26
Issue number7
Early online date28 Mar 2018
DOIs
Publication statusPublished - Jul 2018

Abstract

Pluripotent stem cell-derived differentiated endothelial cells offer high potential in regenerative medicine in the cardiovascular system. With the aim of translating the use of a human stem cell-derived endothelial cell product (hESC-ECP) for treatment of critical limb ischemia (CLI) in man, we report a GMP-compatible protocol and detailed cell tracking and efficacy data in multiple pre-clinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP which were identified as mostly endothelial (60% CD31+/CD144+), with the remainder of the subset expressing various pericyte/mesenchymal stem cell markers. Cell tracking using MRI, PET and qPCR in a murine model of limb ischemia demonstrated that hESC-ECP were detectable up to day 7 following injection. Efficacy in several murine models of limb ischemia (immunocompromised/immunocompetent mice and mice with either Type I/II diabetes mellitus) demonstrated significantly increased blood perfusion and capillary density. Overall, we demonstrate a GMP-compatible hESC-ECP that improved ischemic limb perfusion and increased local angiogenesis without engraftment, paving the way for translation of this therapy.

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