Mesenchymal stromal cells cultured in physiological conditions sustain citrate secretion with glutamate anaplerosis
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.
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
Publication
Molecular Metabolism
Status
Peer reviewed
ISSN
2212-8778Type
Journal article
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".Collections
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.