Derivation of endothelial cells from human embryonic stem cells by directed differentiation: analysis of microRNA and angiogenesis in vitro and in vivo

Kane, N. M., Meloni, M., Spencer, H. L., Craig, M. A., Strehl, R., Milligan, G., Houslay, M. D., Mountford, J. C., Emanueli, C. and Baker, A. H. (2010) Derivation of endothelial cells from human embryonic stem cells by directed differentiation: analysis of microRNA and angiogenesis in vitro and in vivo. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(7), pp. 1389-1397. (doi:10.1161/ATVBAHA.110.204800)

Kane, N. M., Meloni, M., Spencer, H. L., Craig, M. A., Strehl, R., Milligan, G., Houslay, M. D., Mountford, J. C., Emanueli, C. and Baker, A. H. (2010) Derivation of endothelial cells from human embryonic stem cells by directed differentiation: analysis of microRNA and angiogenesis in vitro and in vivo. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(7), pp. 1389-1397. (doi:10.1161/ATVBAHA.110.204800)

Full text not currently available from Enlighten.

Abstract

<b>Objective</b>: To develop an embryoid body-free directed differentiation protocol for the rapid generation of functional vascular endothelial cells derived from human embryonic stem cells (hESCs) and to assess the system for microRNA regulation and angiogenesis.<p></p> <b>Methods and Results</b>: The production of defined cell lineages from hESCs is a critical requirement for evaluating their potential in regenerative medicine. We developed a feeder- and serum-free protocol. Directed endothelial differentiation of hESCs revealed rapid loss of pluripotency markers and progressive induction of mRNA and protein expression of vascular markers (including CD31 and vascular endothelial [VE]-cadherin) and angiogenic growth factors (including vascular endothelial growth factor), increased expression of angiogenesis-associated microRNAs (including miR-126 and miR-210), and induction of endothelial cell morphological features. In vitro, differentiated cells produced nitric oxide, migrated across a wound, and formed tubular structures in both the absence and the presence of 3D matrices (Matrigel). In vivo, we showed that cells that differentiated for 10 days before implantation were efficient at the induction of therapeutic neovascularization and that hESC-derived cells were incorporated into the blood-perfused vasculature of recipient mice.<p></p> <b>Conclusion</b>: The directed differentiation of hESCs is efficient and effective for the differentiation of functional endothelial cells from hESCs.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Houslay, Professor Miles and Baker, Professor Andrew and Spencer, Miss Helen and Kane, Dr Nicole and Mountford, Dr Joanne and Milligan, Professor Graeme and Craig, Dr Margaret and Meloni, Dr Marco
Authors: Kane, N. M., Meloni, M., Spencer, H. L., Craig, M. A., Strehl, R., Milligan, G., Houslay, M. D., Mountford, J. C., Emanueli, C., and Baker, A. H.
Subjects:Q Science > QR Microbiology
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher:American Heart Association
ISSN:1079-5642
ISSN (Online):1524-4636
Published Online:29 April 2010
Copyright Holders:Copyright © 2010 American Heart Association
First Published:First published in Arteriosclerosis, Thrombosis, and Vascular Biology 30(7):1389-1397
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher
Related URLs:

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
30691Molecular interaction between receptor signal transduction systems involving guanine nucleotide regulatory proteinsMiles HouslayMedical Research Council (MRC)PG8604010Institute of Neuroscience and Psychology
478611Interrogation and manipulation of micro RNA during differentiation of human ES cells to cardiomyocyte and vascular lineagesAndrew BakerBritish Heart Foundation (BHF)PG/08/107/26160RI CARDIOVASCULAR & MEDICAL SCIENCES