Volatile organic compounds (VOCs) to monitor cell expansion and microbial contamination of mesenchymal stromal cells (MSCs): a preliminary study

Several investigations have identified volatile organic compounds (VOCs) as potential biomarkers for the detection and identification of microbial contamination of metabolically active mammalian cell cultures. In this study, we showed that emitted VOCs discriminate between uncontaminated mesenchymal stromal cells (MSCs) and those contaminated with the bacterium<i>Staphylococcus epidermidis</i>or fungus<i>Aspergillus Fumigatus</i>separately,<i>in vitro</i>, using a methodology based on an adapted cell culture and thermal desorption-gas chromatography-mass spectrometry. In addition, we elucidated a set of discriminatory volatile compounds from the MSC cultures and media alone across a time series experiment. Partial least squares-discriminant analysis-variable importance in projection confirmed putative identifications of 18, 16, and 26 VOCs that showed relevant changes in a bacterial, fungal, and universal pathogen model, respectively, with an accuracy of 100% in the fungal model. Among these metabolites, octane, 2,5,6-trimethyl- overlapped between the three groups. Furthermore, a total of 15 VOCs were found most relevant to cell culture expansion over three days based on cluster analysis. This novel study goes a step further in identifying distinct VOC signatures of MSCs contaminated with<i>S. epidermidis</i>or<i>A. fumigatus</i>, and in monitoring MSCs proliferation over time. This pilot study shows preliminary results that indicate that VOC headspace analysis could serve as a suitable, rapid, non-invasive, and non-destructive tool for the metabolic and growth monitoring of MSCs in a dynamic cell culture bioreactor system.