Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study
Mohammad M. Banoei,
Lauralyn A. McIntyre,
Duncan J. Stewart,
Shirley H. J. Mei,
David Courtman,
Irene Watpool,
John Granton,
John Marshall,
Claudia dos Santos,
Keith R. Walley,
Kenny Schlosser,
Dean A. Fergusson,
Brent W. Winston,
on behalf of Canadian Critical Care Trials Group (CCCTG),
on behalf of Canadian Critical Care Translational Biology Group (CCCTBG)
Affiliations
Mohammad M. Banoei
Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada
Lauralyn A. McIntyre
Department of Medicine (Division of Critical Care), University of Ottawa, Ottawa, ON K1H 8L6, Canada
Duncan J. Stewart
Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, Canada
Shirley H. J. Mei
Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, Canada
David Courtman
Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, Canada
Irene Watpool
Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, Canada
John Granton
Department of Medicine, University of Toronto, Toronto, ON M5G 2N2, Canada
John Marshall
Department of Surgery and Critical Care Medicine, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, The University of Toronto, Toronto, ON M5B 1W8, Canada
Claudia dos Santos
Department of Surgery and Critical Care Medicine, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, The University of Toronto, Toronto, ON M5B 1W8, Canada
Keith R. Walley
Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada
Kenny Schlosser
Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, Canada
Dean A. Fergusson
Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, Canada
Brent W. Winston
Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada
on behalf of Canadian Critical Care Trials Group (CCCTG)
on behalf of Canadian Critical Care Translational Biology Group (CCCTBG)
Sepsis is the result of an uncontrolled host inflammatory response to infection that may lead to septic shock with multiorgan failure and a high mortality 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 high mortality. Herein, we explore metabolic 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 without MSC treatment. Serum metabolomics profiling was performed to detect and characterize metabolite changes due to MSC treatment and to help determine the sample size needed for a phase II clinical trial and to define a metabolomic response to MSC treatment. Serum metabolites were measured using 1H-NMR and HILIC-MS at times 0, 24 and 72 h after MSC infusion. The results demonstrated the significant impact of MSC treatment on serum metabolic changes in a dose- and time-dependent manner compared to non-MSC-treated septic shock patients. This study suggests that plasma metabolomics can be used to assess the response to MSC 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 of MSC-treated septic shock patients are related to outcomes of septic shock in the short and long term will need to be explored in a larger adequately powered phase II clinical trial.
