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 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...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | Metabolites |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-1989/13/11/1142 |
| _version_ | 1797458428429336576 |
|---|---|
| author | 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) |
| author_facet | 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) |
| author_sort | Mohammad M. Banoei |
| collection | DOAJ |
| description | 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 <sup>1</sup>H-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. |
| first_indexed | 2024-03-09T16:36:58Z |
| format | Article |
| id | doaj.art-3455d13757b24114a6f29090a6d96d18 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T16:36:58Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-3455d13757b24114a6f29090a6d96d182023-11-24T14:55:28ZengMDPI AGMetabolites2218-19892023-11-011311114210.3390/metabo13111142Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory StudyMohammad M. Banoei0Lauralyn A. McIntyre1Duncan J. Stewart2Shirley H. J. Mei3David Courtman4Irene Watpool5John Granton6John Marshall7Claudia dos Santos8Keith R. Walley9Kenny Schlosser10Dean A. Fergusson11Brent W. Winston12on behalf of Canadian Critical Care Trials Group (CCCTG)on behalf of Canadian Critical Care Translational Biology Group (CCCTBG)Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, CanadaDepartment of Medicine (Division of Critical Care), University of Ottawa, Ottawa, ON K1H 8L6, CanadaOttawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaOttawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaOttawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaOttawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaDepartment of Medicine, University of Toronto, Toronto, ON M5G 2N2, CanadaDepartment 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, CanadaDepartment 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, CanadaCentre for Heart Lung Innovation, University of British Columbia, Vancouver, BC V6Z 1Y6, CanadaOttawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaOttawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaDepartment of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, CanadaSepsis 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 <sup>1</sup>H-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.https://www.mdpi.com/2218-1989/13/11/1142biomarkermesenchymal stem cellsseptic shockclinical trialmetabolomicscell therapy |
| spellingShingle | 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) Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study Metabolites biomarker mesenchymal stem cells septic shock clinical trial metabolomics cell therapy |
| title | Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study |
| title_full | Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study |
| title_fullStr | Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study |
| title_full_unstemmed | Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study |
| title_short | Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study |
| title_sort | metabolomics analysis of mesenchymal stem cell msc therapy in a phase i clinical trial of septic shock an exploratory study |
| topic | biomarker mesenchymal stem cells septic shock clinical trial metabolomics cell therapy |
| url | https://www.mdpi.com/2218-1989/13/11/1142 |
| work_keys_str_mv | AT mohammadmbanoei metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT lauralynamcintyre metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT duncanjstewart metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT shirleyhjmei metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT davidcourtman metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT irenewatpool metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT johngranton metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT johnmarshall metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT claudiadossantos metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT keithrwalley metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT kennyschlosser metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT deanafergusson metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT brentwwinston metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT onbehalfofcanadiancriticalcaretrialsgroupccctg metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy AT onbehalfofcanadiancriticalcaretranslationalbiologygroupccctbg metabolomicsanalysisofmesenchymalstemcellmsctherapyinaphaseiclinicaltrialofsepticshockanexploratorystudy |