No / 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.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/11431 |
| Date | 11 August 2016 |
| Creators | Alakpa, E.V., Jayawarna, V., Lampel, A., Burgess, K.V., West, C.C., Bakker, S.C.J., Roy, S., Javid, Nadeem, 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., Dalby, M.J. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, No full-text in the repository |
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