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 |
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| Affiliation: | 1. Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, Georgia, USA;2. Marcus Center for Therapeutic Cell Characterization and Manufacturing (MC3M), Georgia Institute of Technology, Atlanta, Georgia, USA;3. National Science Foundation Engineering Research Center (ERC) for Cell Manufacturing Technologies (CMaT), Atlanta, Georgia, USA;4. Georgia Tech Research Institute (GTRI), Georgia Institute of Technology, Atlanta, Georgia, USA;1. Graduate Program for Collective Health, Faculty of Health Sciences, University of Brasilia, Brasilia, Brazil;2. Oswaldo Cruz Foundation, Rio de Janeiro, Brazil;3. Departament of Hemotherapy and Cell Therapy, Israelita Albert Einstein Hospital, São Paulo, Brazil;4. Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;5. Postgraduate Program in Health Sciences and Technologies, Faculty of Ceilandia, University of Brasilia, Brasília, Brazil;6. Collective Health School, Faculty of Ceilandia, University of Brasilia, Brasília, Brazil;1. Dirección Técnica de Investigación, Desarrollo e Innovación, Instituto Nacional de Investigación en Salud Pública “Leopoldo Izquieta Pérez"- INSPI,Guayaquil, Ecuador;2. Escuela de Medicina, Colegio de Ciencias de la Salud, Universidad San Francisco de Quito USFQ, Quito, Ecuador;3. Instituto de Investigaciones en Biomedicina iBioMed, Universidad San Francisco de Quito USFQ, Quito, Ecuador;4. Mito-Act Research Consortium, Quito, Ecuador;5. Biología, Colegio de Ciencias Biológicas y Ambientales COCIBA, Universidad San Francisco de Quito USFQ, Quito, Ecuador;6. PhD Program in Biomedicine, Faculty of Medicine, Universidad de los Andes, Santiago, Chile;7. Biología, Pontificia Universidad Católica del Ecuador PUCE, Quito, Ecuador;8. Escuela de Medicina Veterinaria, Colegio de Ciencias de la Salud, Universidad San Francisco de Quito USFQ, Quito, Ecuador;9. Sistemas Médicos SIME, Universidad San Francisco de Quito USFQ, Quito, Ecuador;1. School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China;2. Daxing Research Institute, University of Science and Technology Beijing, Beijing, China;3. Cell Therapy Laboratory, First Hospital of Hebei Medical University, Shijiazhuang, China;4. Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang, China;1. Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China;2. School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China;3. Daxing Research Institute, University of Science and Technology Beijing, Beijing, China;1. School of Biomedical Engineering, University of British Columbia, Vancouver, Canada;2. British Columbia Children''s Hospital Research Institute, Vancouver, Canada;3. Michael Smith Laboratories, University of British Columbia, Vancouver, Canada;4. Department of Surgery, University of British Columbia, Vancouver, Canada;5. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada;6. Department of Molecular Oncology, British Columbia Cancer Research Institute, Vancouver, Canada;7. Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, Canada |
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| Abstract: | Background aimsCell 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.MethodsHere the authors developed an untargeted two-dimensional gas chromatography mass spectrometry (GC×GC-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.ResultsSpecifically, using mesenchymal stromal cell cultures as a model, the authors demonstrated that GC×GC-MS of the culture medium headspace can effectively discriminate between media types and tissue sources. Headspace GC×GC-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.ConclusionsThis work establishes GC×GC-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. |
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