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Olesen 2022 Metabol Open

From Bioblast
Publications in the MiPMap
Olesen K, Moruzzi N, Bulatovic I, Folmes C, Jeon R, Felldin U, Terzic A, Simonson OE, Le Blanc K, Österholm C, Berggren PO, Schiffer T, Rodin S, Tilevik A, Grinnemo KH (2022) Diversity of respiratory parameters and metabolic adaptation to low oxygen tension in mesenchymal stromal cells. https://doi.org/10.1016/j.metop.2022.100167

» Metabol Open 13:100167. PMID: 35528374 Open Access

Olesen Kim, Moruzzi Noah,  Bulatovic Ivana,  Folmes Clifford,  Jeon Ryounghoon,  Felldin Ulrika,  Terzic Andre,  Simonson Oscar E,  Le Blanc Katarina,  Oesterholm Cecilia, Berggren Per-Olof,  Schiffer Tomas,  Rodin Sergey,  Tilevik Andreas,  Grinnemo Karl-Henrik (2022) Metabol Open

Abstract: Cell metabolism has been shown to play an active role in regulation of stemness and fate decision. In order to identify favorable culture conditions for mesenchymal stromal cells (MSCs) prior to transplantation, this study aimed to characterize the metabolic function of MSCs from different developmental stages in response to different oxygen tension during expansion.

We cultured human fetal cardiac MSCs and human adult bone-marrow MSCs for a week under hypoxia (3% O2) and normoxia (20% O2). We performed mitochondrial characterization and assessed oxygen consumption- and extracellular acidification-rates (OCR and ECAR) in addition to oxygen-sensitive respiration and mitochondrial complex activities, using both the Seahorse and Oroboros systems.

Adult and fetal MSCs displayed similar basal respiration and mitochondrial amount, however fetal MSCs had lower spare respiratory capacity and apparent coupling efficiency. Fetal MSCs expanded in either hypoxia or normoxia demonstrated similar acidification rates, while adult MSCs downregulated their aerobic glycolysis in normoxia. Acute decrease in oxygen tension caused a higher respiratory inhibition in adult compared to fetal MSCs. In both sources of MSCs, minor changes in complex activities in normoxic and hypoxic cultures were found.

In contrast to adult MSCs, fetal MSCs displayed similar respiration and aerobic glycolysis at different O2 culture concentrations during expansion. Adult MSCs adjusted their respiration to glycolytic activities, depending on the culture conditions thus displaying a more mature metabolic function. These findings are relevant for establishing optimal in vitro culturing conditions, with the aim to maximize engraftment and therapeutic outcome. Keywords: Aerobic glycolysis, Development, Hypoxia, Mesenchymal stromal cells, Metabolism, Mitochondria Bioblast editor: Plangger M


Labels: MiParea: Respiration 


Organism: Human  Tissue;cell: Other cell lines  Preparation: Permeabilized cells 


Coupling state: LEAK, OXPHOS  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2022-12