Robust Revascularization in Models of Limb Ischemia Using a Clinically Translatable Human Stem Cell-Derived Endothelial Cell Product
Summary
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. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
| Authors | MacAskill MG, Saif J, Condie A, Jansen MA, MacGillivray TJ, Tavares AAS, Fleisinger L, Spencer HL, Besnier M, Martin E, Biglino G, Newby DE, Hadoke PWF, Mountford JC, Emanueli C, Baker AH |
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| Journal | Molecular therapy : the journal of the American Society of Gene Therapy |
| Publication Date | 2018 Jul 5;26(7):1669-1684 |
| PubMed | 29703701 |
| PubMed Central | PMC6035339 |
| DOI | 10.1016/j.ymthe.2018.03.017 |