Identification and characterization of small-molecule ligands that maintain pluripotency of human embryonic stem cells

Burton, P. et al. (2010) Identification and characterization of small-molecule ligands that maintain pluripotency of human embryonic stem cells. Biochemical Society Transactions, 38(4), pp. 1058-1061. (doi:10.1042/BST0381058)

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Abstract

hESCs (human embryonic stem cells) offer great potential for pharmaceutical research and development and, potentially, for therapeutic use. However, improvements in cell culture are urgently required to allow the scalable production of large numbers of cells that maintain pluripotency. Supplementing feeder-free conditions with either EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine] or readily synthesized analogues of this compound maintains hESC pluripotency in the absence of exogenous cytokines. When the hESC lines SA121 or SA461 were maintained in feeder-free conditions with EHNA they displayed no reduction in stem-cell-associated markers such as Nanog, Oct4 (octamer-binding protein 4) and SSEA4 (stage-specific embryonic antigen 4) when compared with cells maintained in full feeder-free conditions that included exogenously added bFGF (basic fibroblast growth factor). Spontaneous differentiation was reversibly suppressed by the addition of EHNA, but EHNA did not limit efficient spontaneous or directed differentiation following its removal. We conclude that EHNA or related compounds offers a viable alternative to exogenous cytokine addition in maintaining hESC cultures in a pluripotent state and might be a particularly useful replacement for bFGF for large-scale or GMP (good manufacturing practice)-compliant processes.

Item Type:Articles
Additional Information:The final version of record is available at http://dx.doi.org/10.1042/BST0381058
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Houslay, Professor Miles and Baillie, Professor George and Baker, Professor Andrew and Burton, Dr Peter and Gilmour, Dr Jane and Kane, Dr Nicole and Mountford, Dr Joanne and McCahill, Dr Angela and McAbney, Mr John and Milligan, Professor Graeme
Authors: Burton, P., Adams, D.R., Abraham, A., Allcock, R.W., Jiang, Z., McCahill, A., Gilmour, J., McAbney, J., Kane, N.M., Baillie, G.S., McKenzie, F.R., Baker, A.H., Houslay, M.D., Mountford, J.C., and Milligan, G.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
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
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Biochemical Society Transactions
Publisher:Portland Press
ISSN:0300-5127
ISSN (Online):1470-8752
Copyright Holders:Copyright © 2010 Biochemical Society
First Published:First published in Biochemical Society Transactions 38(4):1058-1061
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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