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Characterizing Human Mesenchymal Stromal Cells Immune Modulatory Potency Using Targeted Lipidomic Profiling of Sphingolipids

View ORCID ProfileS’Dravious A. DeVeaux, View ORCID ProfileMolly E. Ogle, View ORCID ProfileSofiya Vyshnya, Nathan F. Chiappa, Bobby Leitmann, Ryan Rudy, Abigail Day, View ORCID ProfileLuke J. Mortensen, Joanne Kurtzberg, View ORCID ProfileKrishnendu Roy, View ORCID ProfileEdward A. Botchwey
doi: https://doi.org/10.1101/2021.06.01.446428
S’Dravious A. DeVeaux
1The Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory, Atlanta, GA, United States
2Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, United States
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  • ORCID record for S’Dravious A. DeVeaux
Molly E. Ogle
1The Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory, Atlanta, GA, United States
2Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, United States
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Sofiya Vyshnya
1The Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory, Atlanta, GA, United States
2Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, United States
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Nathan F. Chiappa
1The Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory, Atlanta, GA, United States
2Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, United States
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Bobby Leitmann
3Regenerative Bioscience Center, Rhodes Center for ADS, University of Georgia, Athens, GA, United States
4School of Chemical, Materials and Biomedical Engineering, University of Georgia, Athens, GA, United States
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Ryan Rudy
1The Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory, Atlanta, GA, United States
2Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, United States
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Abigail Day
1The Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory, Atlanta, GA, United States
2Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, United States
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Luke J. Mortensen
3Regenerative Bioscience Center, Rhodes Center for ADS, University of Georgia, Athens, GA, United States
4School of Chemical, Materials and Biomedical Engineering, University of Georgia, Athens, GA, United States
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Joanne Kurtzberg
6Marcus Center for Cellular Cures, Duke University School of Medicine, Durham, NC, United States
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Krishnendu Roy
1The Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory, Atlanta, GA, United States
5Marcus Center for Therapeutic Cell Characterization and Manufacturing, Georgia Institute of Technology, Atlanta, GA, United States
7NSF Engineering Research Center (ERC) for Cell Manufacturing Technologies (CMaT), Georgia Institute of Technology, Atlanta, GA, United States
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  • For correspondence: krish.roy@gatech.edu edward.botchwey@bme.gatech.edu
Edward A. Botchwey
1The Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory, Atlanta, GA, United States
2Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, United States
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  • For correspondence: krish.roy@gatech.edu edward.botchwey@bme.gatech.edu
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ABSTRACT

Cell therapies are expected to increase over the next decade due to increasing demand for clinical applications. Mesenchymal stromal cells (MSCs) have been explored to treat a number of diseases, with some successes in early clinical trials. Despite early successes, poor MSC characterization results in lessened therapeutic capacity once in vivo. Here, we characterized bone–marrow (BM), adipose derived and umbilical cord tissue MSCs’ sphingolipids (SLs), a class of bioactive lipids, using liquid chromatography – tandem mass spectrometry. We found ceramide levels differed based upon donor’s sex in BM-MSCs. We detected fatty acyl chain variants in MSCs from all 3 sources. Principal component analysis showed IFN-γ primed and unstimulated MSCs separated according to their SL signature. We detected higher ceramide levels in low IDO MSCs, indicating sphingomeylinase or ceramidase enzymatic activity may be involved in their immune potency. Lastly, linear discriminant analysis revealed that MSCs separated based on tissue source.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵† Denotes co-first authorship

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Posted June 07, 2021.
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Characterizing Human Mesenchymal Stromal Cells Immune Modulatory Potency Using Targeted Lipidomic Profiling of Sphingolipids
S’Dravious A. DeVeaux, Molly E. Ogle, Sofiya Vyshnya, Nathan F. Chiappa, Bobby Leitmann, Ryan Rudy, Abigail Day, Luke J. Mortensen, Joanne Kurtzberg, Krishnendu Roy, Edward A. Botchwey
bioRxiv 2021.06.01.446428; doi: https://doi.org/10.1101/2021.06.01.446428
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Characterizing Human Mesenchymal Stromal Cells Immune Modulatory Potency Using Targeted Lipidomic Profiling of Sphingolipids
S’Dravious A. DeVeaux, Molly E. Ogle, Sofiya Vyshnya, Nathan F. Chiappa, Bobby Leitmann, Ryan Rudy, Abigail Day, Luke J. Mortensen, Joanne Kurtzberg, Krishnendu Roy, Edward A. Botchwey
bioRxiv 2021.06.01.446428; doi: https://doi.org/10.1101/2021.06.01.446428

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