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 |
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Keywords: | GMP, cell therapy, critical limb ischemia. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Baker, Professor Andrew and Mountford, Dr Joanne |
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 > School of Cardiovascular & Metabolic Health |
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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