Robust revascularization in models of limb ischemia using a clinically translatable human stem cell-derived endothelial cell product (original) (raw)
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)
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 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 |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
1
TRANSLATING HUMAN EMBRYONIC STEM CELL-DERIVED ENDOTHELIAL CELL THERAPY TO THE CLINIC
Andrew Baker
MR/K00719X/1
RI CARDIOVASCULAR & MEDICAL SCIENCES
1
BHF Centre for regenerative medicine
Andrew Baker
RM/13/2/30158
RI CARDIOVASCULAR & MEDICAL SCIENCES
1
BHF Chair of Translational Cardiovascular Sciences
Andrew Baker
CH/11/2/28733
RI CARDIOVASCULAR & MEDICAL SCIENCES
Deposit and Record Details
| ID Code: | 161959 |
|---|---|
| Depositing User: | Publications Router |
| Datestamp: | 10 May 2018 13:18 |
| Last Modified: | 28 May 2020 18:49 |
| Date of acceptance: | 26 March 2018 |
| Date of first online publication: | 28 March 2018 |
| Date Deposited: | 10 May 2018 |
| Data Availability Statement: | No |