Tunable supramolecular hydrogels for selection of lineage-guiding metabolites in stem cell cultures
Alakpa, Enateri V. and Jayawarna, Vineetha and Lampel, Ayala and Burgess, Karl V. and West, Christopher C. and Bakker, Sanne C.J. and Roy, Sangita and Javid, Nadeem and Fleming, Scott and Lamprou, Dimitris A. and Yang, Jingli and Miller, Angela and Urquhart, Andrew J. and Frederix, Pim W.J.M. and Hunt, Neil T. and Péault, Bruno and Ulijn, Rein V. and Dalby, Matthew J. (2016) Tunable supramolecular hydrogels for selection of lineage-guiding metabolites in stem cell cultures. Chem, 1 (2). pp. 298-319. ISSN 2451-9294 (https://doi.org/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.
ORCID iDs
Alakpa, Enateri V., Jayawarna, Vineetha ORCID: https://orcid.org/0000-0002-2936-6634, Lampel, Ayala, Burgess, Karl V., West, Christopher C., Bakker, Sanne C.J., Roy, Sangita, Javid, Nadeem, Fleming, Scott, Lamprou, Dimitris A. ORCID: https://orcid.org/0000-0002-8740-1661, Yang, Jingli, Miller, Angela, Urquhart, Andrew J., Frederix, Pim W.J.M., Hunt, Neil T. ORCID: https://orcid.org/0000-0001-7400-5152, Péault, Bruno, Ulijn, Rein V. ORCID: https://orcid.org/0000-0001-7974-3779 and Dalby, Matthew J.;-
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Item type: Article ID code: 61810 Dates: DateEvent11 August 2016Published27 July 2016Published Online1 July 2016AcceptedSubjects: Science > Chemistry Department: Faculty of Science > Pure and Applied Chemistry
Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Faculty of Science > PhysicsDepositing user: Pure Administrator Date deposited: 18 Sep 2017 11:03 Last modified: 03 Dec 2024 07:02 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/61810