Diversity of respiratory parameters and metabolic adaptation to low oxygen tension in mesenchymal stromal cells

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

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Abstract

Objective: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Original languageEnglish
Article number100167
Pages (from-to)1-6
Number of pages6
JournalMetabolism open
Volume13
Early online date3 Feb 2022
DOIs
Publication statusPublished - 31 Mar 2022

Bibliographical note

© 2022 The Authors.

Keywords

  • Mesenchymal stromal cells
  • Development
  • Aerobic glycolysis
  • Hypoxia
  • Mitochondria
  • Metabolism

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