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.
Original language | English |
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Pages (from-to) | 1669-1684 |
Number of pages | 16 |
Journal | Molecular Therapy |
Volume | 26 |
Issue number | 7 |
DOIs | |
Publication status | Published - 5 Jul 2018 |
Bibliographical note
© 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).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