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

MacAskill, M. G. et al. (2018) Robust revascularization in models of limb ischemia using a clinically translatable human stem cell-derived endothelial cell product. Molecular Therapy, 26(7), pp. 1669-1684. (doi:10.1016/j.ymthe.2018.03.017) (PMID:29703701) (PMCID:PMC6035339)

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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 good manufacturing practice (GMP)-compatible protocol and detailed cell tracking and efficacy data in multiple preclinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP, which was 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 was 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.

Item Type:Articles
Keywords:GMP, cell therapy, critical limb ischemia.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew and Mountford, Dr Jo
Authors: MacAskill, M. G., Saif, J., Condie, A., Jansen, M. A., MacGillivray, T. J., Tavares, A. A.S., Fleisinger, L., Spencer, H. L., Besnier, M., Martin, E., Biglino, G., Newby, D. E., Hadoke, P. W.F., Mountford, J. C., Emanueli, C., and Baker, A. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Molecular Therapy
Publisher:Elsevier (Cell Press)
ISSN:1525-0016
ISSN (Online):1525-0024
Published Online:28 March 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Molecular Therapy 26(7): 1669-1684
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
587191TRANSLATING HUMAN EMBRYONIC STEM CELL-DERIVED ENDOTHELIAL CELL THERAPY TO THE CLINICAndrew BakerMedical Research Council (MRC)MR/K00719X/1RI CARDIOVASCULAR & MEDICAL SCIENCES
637071BHF Centre for regenerative medicineAndrew BakerBritish Heart Foundation (BHF)RM/13/2/30158RI CARDIOVASCULAR & MEDICAL SCIENCES
583361BHF Chair of Translational Cardiovascular SciencesAndrew BakerBritish Heart Foundation (BHF)CH/11/2/28733RI CARDIOVASCULAR & MEDICAL SCIENCES