| Title: | Longitudinal two-dimensional gas chromatography mass spectrometry as a non-destructive at-line monitoring tool during cell manufacturing identifies volatile features correlative to cell product quality |
| Author(s): | Jimenez AC; Heist CA; Navaei M; Yeago C; Roy K; |
| Address: | "Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, Georgia, USA; Marcus Center for Therapeutic Cell Characterization and Manufacturing (MC3M), Georgia Institute of Technology, Atlanta, Georgia, USA; National Science Foundation Engineering Research Center (ERC) for Cell Manufacturing Technologies (CMaT), Atlanta, Georgia, USA. Georgia Tech Research Institute (GTRI), Georgia Institute of Technology, Atlanta, Georgia, USA. Marcus Center for Therapeutic Cell Characterization and Manufacturing (MC3M), Georgia Institute of Technology, Atlanta, Georgia, USA; National Science Foundation Engineering Research Center (ERC) for Cell Manufacturing Technologies (CMaT), Atlanta, Georgia, USA. Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, Georgia, USA; Marcus Center for Therapeutic Cell Characterization and Manufacturing (MC3M), Georgia Institute of Technology, Atlanta, Georgia, USA; National Science Foundation Engineering Research Center (ERC) for Cell Manufacturing Technologies (CMaT), Atlanta, Georgia, USA. Electronic address: krish.roy@gatech.edu" |
| DOI: | 10.1016/j.jcyt.2022.06.001 |
| ISSN/ISBN: | 1477-2566 (Electronic) 1465-3249 (Linking) |
| Abstract: | "BACKGROUND AIMS: Cell therapies have emerged as a potentially transformative therapeutic modality in many chronic and incurable diseases. However, inherent donor and patient variabilities, complex manufacturing processes, lack of well-defined critical quality attributes and unavailability of in-line or at-line process or product analytical technologies result in significant variance in cell product quality and clinical trial outcomes. New approaches for overcoming these challenges are needed to realize the potential of cell therapies. METHODS: Here the authors developed an untargeted two-dimensional gas chromatography mass spectrometry (GCxGC-MS)-based method for non-destructive longitudinal at-line monitoring of cells during manufacturing to discover correlative volatile biomarkers of cell proliferation and end product potency. RESULTS: Specifically, using mesenchymal stromal cell cultures as a model, the authors demonstrated that GCxGC-MS of the culture medium headspace can effectively discriminate between media types and tissue sources. Headspace GCxGC-MS identified specific volatile compounds that showed a strong correlation with cell expansion and product functionality quantified by indoleamine-2,3-dioxygenase and T-cell proliferation/suppression assays. Additionally, the authors discovered increases in specific volatile metabolites when cells were treated with inflammatory stimulation. CONCLUSIONS: This work establishes GCxGC-MS as an at-line process analytical technology for cell manufacturing that could improve culture robustness and may be used to non-destructively monitor culture state and correlate with end product function" |
| Keywords: | Biomarkers *Dioxygenases Gas Chromatography-Mass Spectrometry/methods Humans *Volatile Organic Compounds/analysis/chemistry cell manufacturing mesenchymal stromal cells (MSCs) non-destructive process analytical technology (PAT) two-dimensional gas chromat; |
| Notes: | "MedlineJimenez, Angela C Heist, Christopher A Navaei, Milad Yeago, Carolyn Roy, Krishnendu eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2022/07/27 Cytotherapy. 2022 Nov; 24(11):1136-1147. doi: 10.1016/j.jcyt.2022.06.001. Epub 2022 Jul 23" |
