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

Mark G. Macaskill, Jaimy Saif, Alison Condie, Maurits A. Jansen, Thomas J. MacGillivray, Adriana A.S. Tavares, Lucija Fleisinger, Helen L. Spencer, Marie Besnier, Ernesto Martin, Giovanni Biglino, David E. Newby, Patrick W.F. Hadoke, Joanne C. Mountford, Costanza Emanueli, Andrew H. Baker

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
JournalMolecular Therapy
Volume26
Issue number7
Early online date28 Mar 2018
DOIs
Publication statusPublished - Jul 2018

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