Speaker
Description
The use of mesenchymal stem cells (MSCs) for bone regeneration is a promising alternative to conventional bone grafts. Because local metabolic alterations seem to be critical for bone regeneration, metabolomics (through cell extracts and culture media) may unveil novel information on MSCs osteogenic differentiation,1,2 allowing their behaviour to be understood and potentially guided towards improved osteogenic lineage commitment (e.g. through specific media tailoring).3,4 However, only a few reports have monitored osteogenesis (mass spectrometry approaches predominating compared to nuclear magnetic resonance (NMR) spectroscopy), with scarce information interconecting intracellular and extracellular metabolic alterations.2,5 Here, NMR untargeted metabolomics is applied to monitor endo- and exometabolome adaptations of human adipose tissue-derived MSCs throughout 21 days of osteogenic differentiation. Endometabolome results revealed significant fluctuations in the metabolism of amino acids, energy-related compounds, lipids, nucleotides, and metabolic players in protective anti-oxidative mechanisms. Furthermore, exometabolome data highlighted alanine, glutamate, glycerol and citrate as important secretome components. Different metabolic stages are suggested, supported by putative biochemical explanations, and other important issues (such as inter-donor variability and aging effect) are discussed. Overall, this work has shown the great potential of NMR metabolomics to characterize the dynamic metabolism of MSC osteogenenic differentiation, ultimately enabling the potential discovery of universal biomarkers of osteogenic differentiation efficacy, with potential translation to in vivo clinical practice.
- Loeffler, J. et al., Trends Endocrinol. Metab. 29, 99–110 (2018)
- Bispo, D. S. C. et al., Stem Cell Rev. Reports. 17, 2003–2024 (2021)
- Alakpa, E. V. et al., Chem. 1, 298–319 (2016)
- Hodgkinson, T. et al., Sci. Adv., 7, eabb7921 (2021)
- Surrati, A. et al., Cell. Physiol. Biochem. 55, 311–326 (2021)
Acknowledgements: We acknowledge the Portuguese Foundation for Science and Technology (FCT) for co-funding the BIOIMPLANT project (PTDC/BTM-ORG/28835/2017) through the COMPETE2020 program and European Union fund FEDER (POCI-01-0145-FEDER-028835); CICECO-Aveiro Institute of Materials project (UIDB/50011/2020 & UIDP/50011/2020), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020. DSB acknowledges the Sociedade Portuguesa de Química and FCT for her PhD grant SFRH/BD/150655/2020. The NMR spectrometer used in this work is part of the National NMR Network, partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).
20941805655
