Robust revascularisation in multiple models of limb ischemia using a clinically translatable human stem cell-derived endothelial cell product

Mark G. Macaskill; Jaimy Saif; Alison Condie; Maurits A. Jansen; Thomas J. MacGillivray; Adriana A.S. Tavares; Lucija Fleisinger; Helen L. Spencer; Marie Besnier; Ernesto Martin; Giovanni Biglino; David E. Newby; Patrick W.F. Hadoke; Joanne C. Mountford; Costanza Emanueli; Andrew H. Baker

doi:10.1016/j.ymthe.2018.03.017

Robust revascularisation in multiple models of limb ischemia using a clinically translatable human stem cell-derived endothelial cell product

Mark G. Macaskill, Jaimy Saif, Alison Condie, Maurits A. Jansen, Thomas J. MacGillivray, Adriana A.S. Tavares, Lucija Fleisinger, Helen L. Spencer, Marie Besnier, Ernesto Martin, Giovanni Biglino, David E. Newby, Patrick W.F. Hadoke, Joanne C. Mountford, Costanza Emanueli, Andrew H. Baker

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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 GMP-compatible protocol and detailed cell tracking and efficacy data in multiple pre-clinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP which were 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 were 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
Journal	Molecular Therapy
Volume	26
Issue number	7
Early online date	28 Mar 2018
DOIs	https://doi.org/10.1016/j.ymthe.2018.03.017
Publication status	Published - Jul 2018

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2 Active
3 Finished

The BHF Chair of Cardiology
Newby, D.
UK-based charities
1/08/16 → 31/03/24
Project: Research
BHF Chair Transfer from Glasgow
Baker, A.
UK-based charities
1/10/15 → 31/07/26
Project: Research
CH/09/002/26360 BHF Scholarship Scheme - Salary costs
Newby, D.
UK-based charities
1/10/17 → 31/12/18
Project: Research

Patrick Hadoke
- Patrick.hadokeed.acuk
- Deanery of Biomedical Sciences - Personal Chair of Arterial Remodelling
- Centre for Cardiovascular Science
Person: Academic: Research Active
Adriana Tavares
- adriana.tavaresed.acuk
Person: Academic: Research Active

Cite this

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., & Baker, A. H. (2018). Robust revascularisation in multiple models of limb ischemia using a clinically translatable human stem cell-derived endothelial cell product. Molecular Therapy, 26(7). Advance online publication. https://doi.org/10.1016/j.ymthe.2018.03.017

@article{847e5da5961e4c4e885a63bbad6a67f2,

title = "Robust revascularisation in multiple 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 GMP-compatible protocol and detailed cell tracking and efficacy data in multiple pre-clinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP which were 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 were 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.",

author = "Macaskill, {Mark G.} and Jaimy Saif and Alison Condie and Jansen, {Maurits A.} and MacGillivray, {Thomas J.} and Tavares, {Adriana A.S.} and Lucija Fleisinger and Spencer, {Helen L.} and Marie Besnier and Ernesto Martin and Giovanni Biglino and Newby, {David E.} and Hadoke, {Patrick W.F.} and Mountford, {Joanne C.} and Costanza Emanueli and Baker, {Andrew H.}",

year = "2018",

month = jul,

doi = "10.1016/j.ymthe.2018.03.017",

language = "English",

volume = "26",

journal = "Molecular Therapy",

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publisher = "Cell Press",

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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 2018, 'Robust revascularisation in multiple models of limb ischemia using a clinically translatable human stem cell-derived endothelial cell product', Molecular Therapy, vol. 26, no. 7. https://doi.org/10.1016/j.ymthe.2018.03.017

TY - JOUR

T1 - Robust revascularisation in multiple models of limb ischemia using a clinically translatable human stem cell-derived endothelial cell product

AU - Macaskill, Mark G.

AU - Saif, Jaimy

AU - Condie, Alison

AU - Jansen, Maurits A.

AU - MacGillivray, Thomas J.

AU - Tavares, Adriana A.S.

AU - Fleisinger, Lucija

AU - Spencer, Helen L.

AU - Besnier, Marie

AU - Martin, Ernesto

AU - Biglino, Giovanni

AU - Newby, David E.

AU - Hadoke, Patrick W.F.

AU - Mountford, Joanne C.

AU - Emanueli, Costanza

AU - Baker, Andrew H.

PY - 2018/7

Y1 - 2018/7

N2 - 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 GMP-compatible protocol and detailed cell tracking and efficacy data in multiple pre-clinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP which were 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 were 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.

AB - 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 GMP-compatible protocol and detailed cell tracking and efficacy data in multiple pre-clinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP which were 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 were 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.

U2 - 10.1016/j.ymthe.2018.03.017

DO - 10.1016/j.ymthe.2018.03.017

M3 - Article

SN - 1525-0016

VL - 26

JO - Molecular Therapy

JF - Molecular Therapy

IS - 7

ER -

Robust revascularisation in multiple models of limb ischemia using a clinically translatable human stem cell-derived endothelial cell product

Abstract / Description of output

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Projects

The BHF Chair of Cardiology

BHF Chair Transfer from Glasgow

CH/09/002/26360 BHF Scholarship Scheme - Salary costs

Profiles

Patrick Hadoke

Adriana Tavares

Cite this