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Cell-Based Therapeutics

Advancing Cell Therapeutics via Mass Spectrometry

The NSF Engineering Research Center for Cell Manufacturing Technologies is a multi-disciplinary and multi-university national center with participating labs in multiple departments at Georgia Tech. The center is focused on making cell-based therapeutic manufacturing more reproduceable, cost effective, and high quality. For many of these therapeutics, there is lacking good quality control measurements that can aid in the manufacturing process to produce a potent and effective product. We participate in collaborations that aim to discover new potency and quality indicators in the developed therapies. Current projects are centered on the immunosuppressive potency and senescence of mesenchymal stromal cells (MSCs). These projects utilize ultra-high performance liquid chromatography, ion mobility, imaging mass spectrometry, and high-resolution mass spectrometry to investigate chemical signaling associated with immunosuppression and identify related potency markers, and investigate metabolites associated with senescence. These projects also use machine learning and AI tools to identify chemical markers in very large metabolomics/lipidomics datasets.

MALDI-MSI is typically used to look at the distribution of metabolites or drugs within and between different tissue structures. In cell colonies, it can also be used to examine which compounds are excreted and used for signaling, metabolites associated with different cell morphologies, and heterogeneity within a colony as well single cell metabolomics. Pairing MALDI-MSI with higher spatial resolution techniques, like confocal imaging, presents a multi-modal approach that joins high spatial resolution with metabolic information. (A) Acquisition of single cell lipidomes in two MSC colonies, treated and untreated. (B) MALD-MSI images of a MSC colony

References

(1) Nikitina, A.; Huang, D.; Li, L.; Peterman, N.; Cleavenger, S. E.; Fernández, F. M.; Kemp, M. L. A Co-Registration Pipeline for Multimodal MALDI and Confocal Imaging Analysis of Stem Cell Colonies. J. Am. Soc. Mass Spectrom. 2020, 31 (4), 986–989. https://doi.org/10.1021/jasms.9b00094.

(2) Maughon, T. S.; Shen, X.; Huang, D.; Michael, A. O. A.; Shockey, W. A.; Andrews, S. H.; McRae, J. M.; Platt, M. O.; Fernández, F. M.; Edison, A. S.; Stice, S. L.; Marklein, R. A. Metabolomics and Cytokine Profiling of Mesenchymal Stromal Cells Identify Markers Predictive of T-Cell Suppression. Cytotherapy 2022, 24 (2), 137–148. https://doi.org/10.1016/j.jcyt.2021.08.002.

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CONTACT

Fernández group
Georgia Institute of Technology
School of Chemistry and Biochemistry
ES&T L1244
901 Atlantic Drive Atlanta, GA 30332

Phone: (404) 385-4432
Fax: (404) 894-7452

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