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Mesenchymal stromal cells cultured in physiological conditions sustain citrate secretion with glutamate anaplerosis
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dc.contributor.author | Taurino, Giuseppe | |
dc.contributor.author | Deshmukh, Ruhi | |
dc.contributor.author | Villar, Victor H | |
dc.contributor.author | Chiu, Martina | |
dc.contributor.author | Shaw, Robin | |
dc.contributor.author | Hedley, Ann | |
dc.contributor.author | Shokry, Engy | |
dc.contributor.author | Sumpton, David | |
dc.contributor.author | Dander, Erica | |
dc.contributor.author | D'Amico, Giovanna | |
dc.contributor.author | Bussolati, Ovidio | |
dc.contributor.author | Tardito, Saverio | |
dc.date.accessioned | 2023-08-14T14:30:06Z | |
dc.date.available | 2023-08-14T14:30:06Z | |
dc.date.issued | 2022-09-01 | |
dc.identifier | 292297630 | |
dc.identifier | f6a05c51-6cca-46da-bf75-a86699662964 | |
dc.identifier | 35752287 | |
dc.identifier | 85133228670 | |
dc.identifier.citation | Taurino , G , Deshmukh , R , Villar , V H , Chiu , M , Shaw , R , Hedley , A , Shokry , E , Sumpton , D , Dander , E , D'Amico , G , Bussolati , O & Tardito , S 2022 , ' Mesenchymal stromal cells cultured in physiological conditions sustain citrate secretion with glutamate anaplerosis ' , Molecular Metabolism , vol. 63 , 101532 . https://doi.org/10.1016/j.molmet.2022.101532 | en |
dc.identifier.issn | 2212-8778 | |
dc.identifier.other | PubMedCentral: PMC9254159 | |
dc.identifier.other | ORCID: /0000-0003-2837-5018/work/140361379 | |
dc.identifier.uri | https://hdl.handle.net/10023/28165 | |
dc.description | Funding: This work was funded by Cancer Research UK award A17196 and A31287 (CRUK Beatson Institute), and Cancer Research UK award A23982 (ST). This work was supported by Associazione Italiana Ricerca sul Cancro (project number IG 2019 Id.23354) to G. D’A. GT received an EMBO Short-Term Fellowship (STF_8177) and a research fellowship by MRH funded by Fondazione Cariparma Project “Parma Microbiota". | en |
dc.description.abstract | Bone marrow mesenchymal stromal cells (MSCs) have immunomodulatory and regenerative potential. However, culture conditions govern their metabolic processes and therapeutic efficacy. Here we show that culturing donor-derived MSCs in Plasmax™, a physiological medium with the concentrations of nutrients found in human plasma, supports their proliferation and stemness, and prevents the nutritional stress induced by the conventional medium DMEM. The quantification of the exchange rates of metabolites between cells and medium, untargeted metabolomics, stable isotope tracing and transcriptomic analysis, performed at physiologically relevant oxygen concentrations (1%O2), reveal that MSCs rely on a high rate of glucose to lactate conversion, coupled with parallel anaplerotic fluxes from glutamine and glutamate to support citrate synthesis and secretion. These distinctive traits of MSCs shape the metabolic microenvironment of the bone marrow niche and can influence nutrient cross-talks under physiological and pathological conditions. | |
dc.format.extent | 10 | |
dc.format.extent | 2806189 | |
dc.language.iso | eng | |
dc.relation.ispartof | Molecular Metabolism | en |
dc.subject | Bone marrow cells | en |
dc.subject | Citrates/metabolism | en |
dc.subject | Glucose/metabolism | en |
dc.subject | Glutamic Acid/metabolism | en |
dc.subject | Humans | en |
dc.subject | Mesenchymal stem cells/metabolism | en |
dc.subject | QP Physiology | en |
dc.subject | RC0254 Neoplasms. Tumors. Oncology (including Cancer) | en |
dc.subject | DAS | en |
dc.subject | MCC | en |
dc.subject.lcc | QP | en |
dc.subject.lcc | RC0254 | en |
dc.title | Mesenchymal stromal cells cultured in physiological conditions sustain citrate secretion with glutamate anaplerosis | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis | en |
dc.contributor.institution | University of St Andrews. Cellular Medicine Division | en |
dc.identifier.doi | https://doi.org/10.1016/j.molmet.2022.101532 | |
dc.description.status | Peer reviewed | en |
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