Topic: Systematic Review/Meta-analysis
Mesenchymal Stromal Cell Therapy for Systemic Sepsis in Preclinical Animal Models: A Systematic Review
Katrina J Sullivan, A. Straus, M. Lalu, D. Moher, S. Mei, D. Fergusson, D. Stewart, J. Marshall, M. McLeod, K. Walley, B. Winston, B. Hutton, M. Jazi, L. McIntyre
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada | Department of Surgery and Critical Care Medicine, Keenan Research Centre of the Li KaShing Knowledge Institute, St. Michaels Hospital, University of Toronto, Toronto, Canada | the University of Edinburgh, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom (Great Britain) | Centre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada | Department of Critical Care Medicine, Medicine and Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada | Clinical Epidemiology
Introduction:
Mesenchymal stromal cells (MSCs, ‘adult stem cells’) represent a potential novel treatment for septic shock. Preclinical animal studies of sepsis suggest that MSCs modulate inflammation, enhance bacteria clearance and tissue repair, and reduce organ failure and death1-5. We performed a systematic review and meta-analysis to answer the question, “In preclinical animal models of sepsis what is the effect of MSCs (versus control treatment) on mortality?”.
Objectives: To determine the effect of MSC treatment on mortality in preclinical models of sepsis, as compared to diseased controls.
Methods:
A systematic search of MEDLINE, Embase, BIOSIS and Web of Science was conducted in May 2015 to identify studies that compared the treatment of sepsis with MSCs versus diseased controls in pre–clinical sepsis models. Data were collected for the mortality and for general study characteristics to enable subgroup meta-analyses. Results were pooled and expressed as odds ratios (OR) and 95% confidence intervals (CI) using a random effects model; heterogeneity was measured with the I2 statistic. Methodological quality of included studies was assessed using the Cochrane Risk of Bias tool. A funnel plot was generated for mortality to examine publication bias.
Results:
3114 citations were screened; 41 studies met our inclusion criteria with 18 studies (describing a total of 20 experiments) reporting the primary outcome of mortality. Meta-analysis indicated that treatment of pre-clinical sepsis with MSCs as compared to control significantly reduced the overall odds of mortality (OR 0.27 [95% CI 0.18-0.40], I2=32%) as well as mortality at pre-defined time intervals: ≤2 days (OR 0.31 [95% CI 0.21-0.47], I2=35%), >2 to ≤4 days (OR 0.23 [95% CI 0.13-0.43], I2=41%) and >4 days (OR 0.18 [95% CI 0.11-0.32], I2=0%). Subgroup analyses suggested efficacy is maintained across a range of experimental conditions (e.g. animal characteristics, sepsis model, MSC characteristics, MSC administration, and control group). The Cochrane Risk of Bias items of sequence generation, allocation concealment, and blinding of outcomes assessors were considered unclear for all 18 studies. Funnel plot analysis showed evidence of asymmetry, suggesting potential publication bias.
Conclusion:
Our results indicate that treatment of preclinical systemic sepsis with MSCs reduces the odds of mortality across a range of conditions. However, unclear reporting of Risk of Bias elements and the suggestion of publication bias limit the strength of our conclusions.
References:
1. Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 2007;179(3):1855-1863.
2. Yang H, Wen Y, Bin J, Hou-You Y, Yu-Tong W. Protection of bone marrow mesenchymal stem cells from acute lung injury induced by paraquat poisoning. Clin Toxicol (Phila ) 2011;49(4):298-302.
3. Islam MN, Sun L, Lindert J, Das SR, Bhattacharya J. Restoration of Alveolar Bioenergetics By Bone Marrow-Derived Mesenchymal Stromal Cells. Am J Respir Crit Care Med . 2011.
4. Kim ES, Chang YS, Choi SJ et al. Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells attenuates Escherichia coli-induced acute lung injury in mice. Respir Res 2011;12:108.
5. Krasnodembskaya A, Song Y, Fang X et al. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells 2010;28(12):2229-2238.
Topic: Systematic Review/Meta-analysis
Mesenchymal Stromal Cell Therapy for Systemic Sepsis in Preclinical Animal Models: A Systematic Review
Katrina J Sullivan, A. Straus, M. Lalu, D. Moher, S. Mei, D. Fergusson, D. Stewart, J. Marshall, M. McLeod, K. Walley, B. Winston, B. Hutton, M. Jazi, L. McIntyre
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada | Department of Surgery and Critical Care Medicine, Keenan Research Centre of the Li KaShing Knowledge Institute, St. Michaels Hospital, University of Toronto, Toronto, Canada | the University of Edinburgh, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom (Great Britain) | Centre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada | Department of Critical Care Medicine, Medicine and Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada | Clinical Epidemiology
Introduction:
Mesenchymal stromal cells (MSCs, ‘adult stem cells’) represent a potential novel treatment for septic shock. Preclinical animal studies of sepsis suggest that MSCs modulate inflammation, enhance bacteria clearance and tissue repair, and reduce organ failure and death1-5. We performed a systematic review and meta-analysis to answer the question, “In preclinical animal models of sepsis what is the effect of MSCs (versus control treatment) on mortality?”.
Objectives: To determine the effect of MSC treatment on mortality in preclinical models of sepsis, as compared to diseased controls.
Methods:
A systematic search of MEDLINE, Embase, BIOSIS and Web of Science was conducted in May 2015 to identify studies that compared the treatment of sepsis with MSCs versus diseased controls in pre–clinical sepsis models. Data were collected for the mortality and for general study characteristics to enable subgroup meta-analyses. Results were pooled and expressed as odds ratios (OR) and 95% confidence intervals (CI) using a random effects model; heterogeneity was measured with the I2 statistic. Methodological quality of included studies was assessed using the Cochrane Risk of Bias tool. A funnel plot was generated for mortality to examine publication bias.
Results:
3114 citations were screened; 41 studies met our inclusion criteria with 18 studies (describing a total of 20 experiments) reporting the primary outcome of mortality. Meta-analysis indicated that treatment of pre-clinical sepsis with MSCs as compared to control significantly reduced the overall odds of mortality (OR 0.27 [95% CI 0.18-0.40], I2=32%) as well as mortality at pre-defined time intervals: ≤2 days (OR 0.31 [95% CI 0.21-0.47], I2=35%), >2 to ≤4 days (OR 0.23 [95% CI 0.13-0.43], I2=41%) and >4 days (OR 0.18 [95% CI 0.11-0.32], I2=0%). Subgroup analyses suggested efficacy is maintained across a range of experimental conditions (e.g. animal characteristics, sepsis model, MSC characteristics, MSC administration, and control group). The Cochrane Risk of Bias items of sequence generation, allocation concealment, and blinding of outcomes assessors were considered unclear for all 18 studies. Funnel plot analysis showed evidence of asymmetry, suggesting potential publication bias.
Conclusion:
Our results indicate that treatment of preclinical systemic sepsis with MSCs reduces the odds of mortality across a range of conditions. However, unclear reporting of Risk of Bias elements and the suggestion of publication bias limit the strength of our conclusions.
References:
1. Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 2007;179(3):1855-1863.
2. Yang H, Wen Y, Bin J, Hou-You Y, Yu-Tong W. Protection of bone marrow mesenchymal stem cells from acute lung injury induced by paraquat poisoning. Clin Toxicol (Phila ) 2011;49(4):298-302.
3. Islam MN, Sun L, Lindert J, Das SR, Bhattacharya J. Restoration of Alveolar Bioenergetics By Bone Marrow-Derived Mesenchymal Stromal Cells. Am J Respir Crit Care Med . 2011.
4. Kim ES, Chang YS, Choi SJ et al. Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells attenuates Escherichia coli-induced acute lung injury in mice. Respir Res 2011;12:108.
5. Krasnodembskaya A, Song Y, Fang X et al. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells 2010;28(12):2229-2238.
Topic: Systematic Review/Meta-analysis
Mesenchymal Stromal Cell Therapy for Systemic Sepsis in Preclinical Animal Models: A Systematic Review
Katrina J Sullivan, A. Straus, M. Lalu, D. Moher, S. Mei, D. Fergusson, D. Stewart, J. Marshall, M. McLeod, K. Walley, B. Winston, B. Hutton, M. Jazi, L. McIntyre
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada | Department of Surgery and Critical Care Medicine, Keenan Research Centre of the Li KaShing Knowledge Institute, St. Michaels Hospital, University of Toronto, Toronto, Canada | the University of Edinburgh, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom (Great Britain) | Centre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada | Department of Critical Care Medicine, Medicine and Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada | Clinical Epidemiology
Introduction:
Mesenchymal stromal cells (MSCs, ‘adult stem cells’) represent a potential novel treatment for septic shock. Preclinical animal studies of sepsis suggest that MSCs modulate inflammation, enhance bacteria clearance and tissue repair, and reduce organ failure and death1-5. We performed a systematic review and meta-analysis to answer the question, “In preclinical animal models of sepsis what is the effect of MSCs (versus control treatment) on mortality?”.
Objectives: To determine the effect of MSC treatment on mortality in preclinical models of sepsis, as compared to diseased controls.
Methods:
A systematic search of MEDLINE, Embase, BIOSIS and Web of Science was conducted in May 2015 to identify studies that compared the treatment of sepsis with MSCs versus diseased controls in pre–clinical sepsis models. Data were collected for the mortality and for general study characteristics to enable subgroup meta-analyses. Results were pooled and expressed as odds ratios (OR) and 95% confidence intervals (CI) using a random effects model; heterogeneity was measured with the I2 statistic. Methodological quality of included studies was assessed using the Cochrane Risk of Bias tool. A funnel plot was generated for mortality to examine publication bias.
Results:
3114 citations were screened; 41 studies met our inclusion criteria with 18 studies (describing a total of 20 experiments) reporting the primary outcome of mortality. Meta-analysis indicated that treatment of pre-clinical sepsis with MSCs as compared to control significantly reduced the overall odds of mortality (OR 0.27 [95% CI 0.18-0.40], I2=32%) as well as mortality at pre-defined time intervals: ≤2 days (OR 0.31 [95% CI 0.21-0.47], I2=35%), >2 to ≤4 days (OR 0.23 [95% CI 0.13-0.43], I2=41%) and >4 days (OR 0.18 [95% CI 0.11-0.32], I2=0%). Subgroup analyses suggested efficacy is maintained across a range of experimental conditions (e.g. animal characteristics, sepsis model, MSC characteristics, MSC administration, and control group). The Cochrane Risk of Bias items of sequence generation, allocation concealment, and blinding of outcomes assessors were considered unclear for all 18 studies. Funnel plot analysis showed evidence of asymmetry, suggesting potential publication bias.
Conclusion:
Our results indicate that treatment of preclinical systemic sepsis with MSCs reduces the odds of mortality across a range of conditions. However, unclear reporting of Risk of Bias elements and the suggestion of publication bias limit the strength of our conclusions.
References:
1. Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 2007;179(3):1855-1863.
2. Yang H, Wen Y, Bin J, Hou-You Y, Yu-Tong W. Protection of bone marrow mesenchymal stem cells from acute lung injury induced by paraquat poisoning. Clin Toxicol (Phila ) 2011;49(4):298-302.
3. Islam MN, Sun L, Lindert J, Das SR, Bhattacharya J. Restoration of Alveolar Bioenergetics By Bone Marrow-Derived Mesenchymal Stromal Cells. Am J Respir Crit Care Med . 2011.
4. Kim ES, Chang YS, Choi SJ et al. Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells attenuates Escherichia coli-induced acute lung injury in mice. Respir Res 2011;12:108.
5. Krasnodembskaya A, Song Y, Fang X et al. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells 2010;28(12):2229-2238.
Topic: Systematic Review/Meta-analysis
Mesenchymal Stromal Cell Therapy for Systemic Sepsis in Preclinical Animal Models: A Systematic Review
Katrina J Sullivan, A. Straus, M. Lalu, D. Moher, S. Mei, D. Fergusson, D. Stewart, J. Marshall, M. McLeod, K. Walley, B. Winston, B. Hutton, M. Jazi, L. McIntyre
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada | Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada | Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada | Department of Surgery and Critical Care Medicine, Keenan Research Centre of the Li KaShing Knowledge Institute, St. Michaels Hospital, University of Toronto, Toronto, Canada | the University of Edinburgh, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom (Great Britain) | Centre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada | Department of Critical Care Medicine, Medicine and Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada | Clinical Epidemiology
Introduction:
Mesenchymal stromal cells (MSCs, ‘adult stem cells’) represent a potential novel treatment for septic shock. Preclinical animal studies of sepsis suggest that MSCs modulate inflammation, enhance bacteria clearance and tissue repair, and reduce organ failure and death1-5. We performed a systematic review and meta-analysis to answer the question, “In preclinical animal models of sepsis what is the effect of MSCs (versus control treatment) on mortality?”.
Objectives: To determine the effect of MSC treatment on mortality in preclinical models of sepsis, as compared to diseased controls.
Methods:
A systematic search of MEDLINE, Embase, BIOSIS and Web of Science was conducted in May 2015 to identify studies that compared the treatment of sepsis with MSCs versus diseased controls in pre–clinical sepsis models. Data were collected for the mortality and for general study characteristics to enable subgroup meta-analyses. Results were pooled and expressed as odds ratios (OR) and 95% confidence intervals (CI) using a random effects model; heterogeneity was measured with the I2 statistic. Methodological quality of included studies was assessed using the Cochrane Risk of Bias tool. A funnel plot was generated for mortality to examine publication bias.
Results:
3114 citations were screened; 41 studies met our inclusion criteria with 18 studies (describing a total of 20 experiments) reporting the primary outcome of mortality. Meta-analysis indicated that treatment of pre-clinical sepsis with MSCs as compared to control significantly reduced the overall odds of mortality (OR 0.27 [95% CI 0.18-0.40], I2=32%) as well as mortality at pre-defined time intervals: ≤2 days (OR 0.31 [95% CI 0.21-0.47], I2=35%), >2 to ≤4 days (OR 0.23 [95% CI 0.13-0.43], I2=41%) and >4 days (OR 0.18 [95% CI 0.11-0.32], I2=0%). Subgroup analyses suggested efficacy is maintained across a range of experimental conditions (e.g. animal characteristics, sepsis model, MSC characteristics, MSC administration, and control group). The Cochrane Risk of Bias items of sequence generation, allocation concealment, and blinding of outcomes assessors were considered unclear for all 18 studies. Funnel plot analysis showed evidence of asymmetry, suggesting potential publication bias.
Conclusion:
Our results indicate that treatment of preclinical systemic sepsis with MSCs reduces the odds of mortality across a range of conditions. However, unclear reporting of Risk of Bias elements and the suggestion of publication bias limit the strength of our conclusions.
References:
1. Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 2007;179(3):1855-1863.
2. Yang H, Wen Y, Bin J, Hou-You Y, Yu-Tong W. Protection of bone marrow mesenchymal stem cells from acute lung injury induced by paraquat poisoning. Clin Toxicol (Phila ) 2011;49(4):298-302.
3. Islam MN, Sun L, Lindert J, Das SR, Bhattacharya J. Restoration of Alveolar Bioenergetics By Bone Marrow-Derived Mesenchymal Stromal Cells. Am J Respir Crit Care Med . 2011.
4. Kim ES, Chang YS, Choi SJ et al. Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells attenuates Escherichia coli-induced acute lung injury in mice. Respir Res 2011;12:108.
5. Krasnodembskaya A, Song Y, Fang X et al. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells 2010;28(12):2229-2238.
