MacAskill, Mark G, Saif, Jaimy, Condie, Alison, Jansen, Maurits A, MacGillivray, Thomas J, Tavares, Adriana A S, Fleisinger, Lucija, Spencer, Helen L, Besnier, Marie, Martin, Ernesto, Biglino, Giovanni, Newby, David E, Hadoke, Patrick W F, Mountford, Joanne C, Emanueli, Costanza and Baker, Andrew H (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.
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.
Publication DOI: | https://doi.org/10.1016/j.ymthe.2018.03.017 |
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Divisions: | College of Health & Life Sciences > Aston Medical School |
Additional Information: | © 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Uncontrolled Keywords: | Animals,Biomarkers/metabolism,Cell Differentiation/physiology,Cell Line,Embryonic Stem Cells/cytology,Endothelial Cells/cytology,Hindlimb/cytology,Humans,Ischemia/metabolism,Mesenchymal Stem Cells/cytology,Mice,Neovascularization, Physiologic/physiology,Pericytes/cytology,Pluripotent Stem Cells/cytology,Stem Cell Transplantation/methods |
Publication ISSN: | 1525-0016 |
Last Modified: | 06 Aug 2024 08:36 |
Date Deposited: | 16 Sep 2019 14:52 |
Full Text Link: | |
Related URLs: |
https://www.sci ... 1448?via%3Dihub
(Publisher URL) |
PURE Output Type: | Article |
Published Date: | 2018-07-05 |
Accepted Date: | 2018-03-26 |
Authors: |
MacAskill, Mark G
Saif, Jaimy Condie, Alison Jansen, Maurits A MacGillivray, Thomas J Tavares, Adriana A S Fleisinger, Lucija Spencer, Helen L Besnier, Marie Martin, Ernesto Biglino, Giovanni Newby, David E Hadoke, Patrick W F Mountford, Joanne C Emanueli, Costanza Baker, Andrew H |