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Intact Cell Mass Spectrometry: Quality Control for Human Embryonic Stem Cells?



Review of “Intact Cell Mass Spectrometry as a Quality Control Tool for Revealing Minute Phenotypic Changes of Cultured Human Embryonic Stem Cells” from STEM CELLS Translational Medicine by Stuart P. Atkinson

As we move closer to the industrial scale culture of stem cells required for application as part of a wide-range of regenerative/reparative strategies, quality control (QC) of the cells involved becomes a pressing concern. Researchers from the laboratory of Aleš Hampl (Masaryk University, Brno, Czech Republic) have recognized this requirement and set out to test a mass spectrometry (MS)-based strategy [1, 2] as a robust, but relatively simple means to ensure the safety and effectiveness of stem cell-based therapies [3]. Their new STEM CELLS Translational Medicine now reports that the capture of intact cell mass spectra “fingerprints” by MS offers an effective means to monitor and quality-control cultures of human embryonic stem cells (hESCs) [4].

Vaňhara et al. first tested their approach by comparing the intact cell MS spectra fingerprints associated with hESCs of different passage number in the knowledge that, while these cells appear morphologically uniform and may express similar levels of specific markers, they can behave very differently. Excitingly, the complex MS fingerprints generated supplied sufficient information to discriminate “young and healthy” hESCs and those “older” hESCs that have likely undergone severe long-term culture adaptation [5] and picked up chromosomal abnormalities. Additionally, the authors also employed MS spectra analysis to differentiate between hESCs cultured under self-renewing conditions and those differentiated towards an ectodermal fate by addition of retinoic acid for 12, 24, or 48 hours, even though these cells possessed a typical uniform morphology and maintained high levels of pluripotency-associated transcription factor expression.

Currently employed QC approaches, which include short tandem repeat (STR) or gene expression profiling  or phenotype monitoring only focus on a limited set of variables, and therefore have limited scope. Will wide-ranging MS spectra analysis replace these limited approaches for routine cell identification/characterization, as the go-to technique for simple, robust, and hypothesis-free hESC QC analysis? Stay tuned to the Stem Cells Portal to find out!


  1. Croxatto A, Prod'hom G, and Greub G, Applications of MALDI-TOF mass spectrometry in clinical diagnostic microbiology. FEMS Microbiology Reviews 2012;36:380-407.
  2. Munteanu B, von Reitzenstein C, Hansch GM, et al., Sensitive, robust and automated protein analysis of cell differentiation and of primary human blood cells by intact cell MALDI mass spectrometry biotyping. Anal Bioanal Chem 2012;404:2277-86.
  3. Valletta E, Kučera L, Prokeš L, et al., Multivariate Calibration Approach for Quantitative Determination of Cell-Line Cross Contamination by Intact Cell Mass Spectrometry and Artificial Neural Networks. PLOS ONE 2016;11:e0147414.
  4. Vaňhara P, Kučera L, Prokeš L, et al., Intact Cell Mass Spectrometry as a Quality Control Tool for Revealing Minute Phenotypic Changes of Cultured Human Embryonic Stem Cells. STEM CELLS Translational Medicine 2018;7:109-114.
  5. Harrison NJ, Baker D, and Andrews PW, The Significance of Culture Adaptation of Embryonic Stem Cells for Regenerative Medicine, in Advances in Stem Cell Research, H. Baharvand and N. Aghdami, Editors. 2012, Humana Press: Totowa, NJ. p. 17-27.