Characterizing human mesenchymal stromal cells’ immune-modulatory potency using targeted lipidomic profiling of sphingolipids

Cell therapies are expected to increase over the next decade owing 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 resul...

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Bibliographic Details
Published in:Cytotherapy (Oxford, England) England), 2022-06, Vol.24 (6), p.608-618
Main Authors: DeVeaux, S'Dravious A., Ogle, Molly E., Vyshnya, Sofiya, Chiappa, Nathan F., Leitmann, Bobby, Rudy, Ryan, Day, Abigail, Mortensen, Luke J., Kurtzberg, Joanne, Roy, Krishnendu, Botchwey, Edward A.
Format: Article
Language:English
Subjects:
Adipose Tissue
adipose-derived mesenchymal stromal cells
Bone Marrow Cells
bone marrow–derived mesenchymal stromal cells
Cell Differentiation
cell manufacturing
Cell Proliferation
Cells, Cultured
Ceramides
Humans
immune potency
Lipidomics
Mesenchymal Stem Cells
Sphingolipids
umbilical cord tissue–derived mesenchymal stromal cells
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Summary:Cell therapies are expected to increase over the next decade owing 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 MSCs derived from bone marrow (BM), adipose tissue and umbilical cord tissue for sphingolipids (SLs), a class of bioactive lipids, using liquid chromatography/tandem mass spectrometry. We found that ceramide levels differed based on the donor's sex in BM-MSCs. We detected fatty acyl chain variants in MSCs from all three sources. Linear discriminant analysis revealed that MSCs separated based on tissue source. Principal component analysis showed that interferon-γ–primed and unstimulated MSCs separated according to their SL signature. Lastly, we detected higher ceramide levels in low indoleamine 2,3-dioxygenase MSCs, indicating that sphingomyelinase or ceramidase enzymatic activity may be involved in their immune potency.
ISSN:1465-3249
1477-2566
DOI:10.1016/j.jcyt.2021.12.009