4.3 Review

Metabolomic Applications in Stem Cell Research: a Review

Journal

STEM CELL REVIEWS AND REPORTS
Volume 17, Issue 6, Pages 2003-2024

Publisher

SPRINGER
DOI: 10.1007/s12015-021-10193-z

Keywords

Stem cells; Biomaterials; Tissue regeneration; Metabolomics; Metabonomics; Nuclear magnetic resonance; Mass spectrometry; Metabolite profiling

Funding

  1. Portuguese Foundation for Science and Technology (FCT) [PTDC/BTM-ORG/28835/2017]
  2. European Union fund FEDER [POCI-01-0145FEDER-028835]
  3. University of Aveiro
  4. Sociedade Portuguesa de Quimica
  5. FCT [SFRH/BD/150655/2020]
  6. CICECO-Aveiro Institute of Materials project by national funds through the FCT/MEC [UIDB/50011/2020, UIDP/50011/2020]
  7. FEDER
  8. FEDER through COMPETE 2020, POCI and PORL [022161]
  9. FCT through PIDDAC
  10. Fundação para a Ciência e a Tecnologia [SFRH/BD/150655/2020, PTDC/BTM-ORG/28835/2017] Funding Source: FCT

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This review describes the use of metabolomics to study stem cell characteristics and function, particularly focusing on developments in the past five years. The analysis covers various aspects of mesenchymal SC behavior, followed by pluripotent and neural SCs, with a few reports addressing other SC types, demonstrating the potential of metabolomics in understanding SC behavior.
This review describes the use of metabolomics to study stem cell (SC) characteristics and function, excluding SCs in cancer research, suited to a fully dedicated text. The interest in employing metabolomics in SC research has consistently grown and emphasis is, here, given to developments reported in the past five years. This text informs on the existing methodologies and their complementarity regarding the information provided, comprising untargeted/targeted approaches, which couple mass spectrometry or nuclear magnetic resonance spectroscopy with multivariate analysis (and, in some cases, pathway analysis and integration with other omics), and more specific analytical approaches, namely isotope tracing to highlight particular metabolic pathways, or in tandem microscopic strategies to pinpoint characteristics within a single cell. The bulk of this review covers the existing applications in various aspects of mesenchymal SC behavior, followed by pluripotent and neural SCs, with a few reports addressing other SC types. Some of the central ideas investigated comprise the metabolic/biological impacts of different tissue/donor sources and differentiation conditions, including the importance of considering 3D culture environments, mechanical cues and/or media enrichment to guide differentiation into specific lineages. Metabolomic analysis has considered cell endometabolomes and exometabolomes (fingerprinting and footprinting, respectively), having measured both lipid species and polar metabolites involved in a variety of metabolic pathways. This review clearly demonstrates the current enticing promise of metabolomics in significantly contributing towards a deeper knowledge on SC behavior, and the discovery of new biomarkers of SC function with potential translation to in vivo clinical practice.

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