Derivation of vascular endothelial cells from human embryonic stem cells under GMP-compliant conditions: towards clinical studies in ischaemic disease

Kaupisch, A., Kennedy, L., Stelmanis, V., Tye, B., Kane, N.M., Mountford, J.C., Courtney, A. and Baker, A.H. (2012) Derivation of vascular endothelial cells from human embryonic stem cells under GMP-compliant conditions: towards clinical studies in ischaemic disease. Journal of Cardiovascular Translational Research, 5(5), pp. 605-617. (doi:10.1007/s12265-012-9379-2)

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Publisher's URL: http://dx.doi.org/10.1007/s12265-012-9379-2

Abstract

Revascularisation of ischaemic tissue remains an area of substantial unmet clinical need in cardiovascular disease. Strategies to induce therapeutic angiogenesis are therefore attractive. Our recent focus has been on human embryonic stem cell (hESC) strategies since hESC can be maintained in a pluripotent state or differentiated into any desired cell type, including endothelial cells (EC), under defined differentiation culture conditions. We recently published a protocol for non-good manufacturing practice (GMP) feeder- and serum-free hESC-EC-directed monolayer differentiation to vascular EC demonstrating the potential to generate hESC-derived EC in a GMP-compliant manner suitable for use in clinical trials. In this study we modified that laboratory protocol to GMP compliance. EC production was confirmed by flow cytometry, qRT-PCR and production of vascular structures in Matrigel®, yielding approximately 30 % mature VE-cadherin+/PECAM-1+ cells using the GMP-compliant hESC line RC13. In conclusion, we have successfully demonstrated the production of vascular EC under GMP-compliant conditions suitable for clinical evaluation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew and Kane, Dr Nicole and Mountford, Dr Joanne and Kaupisch, Dr Alexandra
Authors: Kaupisch, A., Kennedy, L., Stelmanis, V., Tye, B., Kane, N.M., Mountford, J.C., Courtney, A., and Baker, A.H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Journal of Cardiovascular Translational Research
Publisher:Springer Verlag
ISSN:1937-5387
ISSN (Online):1937-5395
Published Online:02 August 2012
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
487811Induced pluripoptent cells: analysis of cell reprogramming of dermal fibroblasts derived from patients with disease vs age-matched healthy controlsAndrew BakerBritish Heart Foundation (BHF)PG/09/007/26675RI CARDIOVASCULAR & MEDICAL SCIENCES