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

Abstract

ABSTRACTCell 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. Linear discriminant analysis revealed that MSCs separated based on tissue source. Principal component analysis showed IFN-γ primed and unstimulated MSCs separated according to their SL signature. Lastly, we detected higher ceramide levels in low IDO MSCs, indicating sphingomeylinase or ceramidase enzymatic activity may be involved in their immune potency.