Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study

Sepsis is the result of an uncontrolled host inflammatory response to infection thatmay lead to septic shock withmultiorgan failure and a highmortality rate. There is an urgent need to improve early diagnosis and to find markers identifying those who will develop septic shock and certainly a need to develop targeted treatments to prevent septic shock and its highmortality. Herein, we exploremetabolic alterations due to mesenchymal stromal cell (MSC) treatment of septic shock. The clinical findings for this study were already reported; MSC therapy was well-tolerated and safe in patients in this phase I clinical trial. In this exploratory metabolomics study, 9 out of 30 patients received an escalating dose of MSC treatment, while 21 patients were withoutMSC treatment. Serum metabolomics profiling was performed to detect and characterizemetabolite changes due toMSC treatment and to help determine the sample size needed for a phase II clinical trial and to define ametabolomic response toMSC treatment. Serum metabolites were measured using H-1-NMR and HILIC-MS at times 0, 24 and 72 h after MSC infusion. The results demonstrated the significant impact ofMSC treatment on serum metabolic changes in a dose- and time-dependent manner compared to non-MSC-treated septic shock patients. This study suggests that plasmametabolomics can be used to assess the response toMSC therapy and that treatment-related metabolomics effects can be used to help determine the sample size needed in a phase II trial. As this study was not powered to detect outcome, how the treatment-induced metabolomic changes described in this study ofMSC-treated septic shock patients are related to outcomes of septic shock in the short and long termwill need to be explored in a larger adequately powered phase II clinical trial.