Robust Revascularization in Models of Limb Ischemia Using a Clinically Translatable Human Stem Cell-Derived Endothelial Cell Product

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
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
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

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