Tunable supramolecular hydrogels for selection of lineage guiding metabolites in stem cell cultures

Alakpa, E. et al. (2016) Tunable supramolecular hydrogels for selection of lineage guiding metabolites in stem cell cultures. Chem, 1(2), pp. 298-319. (doi:10.1016/j.chempr.2016.07.001)

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Abstract

Stem cells are known to differentiate in response to the chemical and mechanical properties of the substrates on which they are cultured. Thus, supramolecular biomaterials with tunable properties are well suited for the study of stem cell differentiation. In this report, we exploited this phenomenon by combining stem cell differentiation in hydrogels with variable stiffness and metabolomics analysis to identify specific bioactive lipids that are uniquely used up during differentiation. To achieve this, we cultured perivascular stem cells on supramolecular peptide gels of different stiffness, and metabolite depletion followed. On soft (1 kPa), stiff (13 kPa), and rigid (32 kPa) gels, we observed neuronal, chondrogenic, and osteogenic differentiation, respectively, showing that these stem cells undergo stiffness-directed fate selection. By analyzing concentration variances of >600 metabolites during differentiation on the stiff and rigid gels (and focusing on chondrogenesis and osteogenesis as regenerative targets, respectively), we identified that specific lipids (lysophosphatidic acid and cholesterol sulfate, respectively), were significantly depleted. We propose that these metabolites are therefore involved in the differentiation process. In order to unequivocally demonstrate that the lipid metabolites that we identified play key roles in driving differentiation, we subsequently demonstrated that these individual lipids can, when fed to standard stem cell cultures, induce differentiation toward chondrocyte and osteoblast phenotypes. Our concept exploits the design of supramolecular biomaterials as a strategy for discovering cell-directing bioactive metabolites of therapeutic relevance.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Burgess, Dr Karl and Miller, Mrs Angela and Yang, Dr Jingli and Alakpa, Miss Enateri and Dalby, Professor Matthew
Authors: Alakpa, E., Jayawama, V., Lampel, A., Burgess, K., West, C. C., Bakker, S. C.J., Roy, S., Javid, N., Fleming, S., Lamprou, D. A., Yang, J., Miller, A., Urquhart, A. J., Frederix, P. W.J.M., Hunt, N. T., Peault, B., Ulijn, R. V., and Dalby, M. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Science and Engineering > School of Geographical and Earth Sciences
Journal Name:Chem
Publisher:Elsevier (Cell Press)
ISSN:2451-9294
Published Online:27 July 2016
Copyright Holders:Copyright © 2016 Elsevier (Cell Press)
First Published:First published in Chem 1(2):298-319
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
608751Dynamic surfaces to mimic mesenchymal stem cell niche functionsMatthew DalbyBiotechnology and Biological Sciences Research Council (BBSRC)BB/K006908/1RI MOLECULAR CELL & SYSTEMS BIOLOGY