Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cell Therapy in Preclinical Models of Sepsis: A Systematic Review and Meta-analysis

Christine Hum; Usama Tahir; Shirley H J Mei; Josee Champagne; Dean A Fergusson; Manoj Lalu; Duncan J Stewart; Keith Walley; John Marshall; Claudia C Dos Santos; Brent W Winston; Asher A Mendelson; Chintan Dave; Lauralyn McIntyre

doi:10.1093/stcltm/szae003

Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cell Therapy in Preclinical Models of Sepsis: A Systematic Review and Meta-analysis

Stem Cells Transl Med. 2024 Apr 15;13(4):346-361. doi: 10.1093/stcltm/szae003.

Authors

Christine Hum¹, Usama Tahir², Shirley H J Mei³, Josee Champagne¹, Dean A Fergusson^{1

4}, Manoj Lalu^{1

3

5

6}, Duncan J Stewart^{3

5}, Keith Walley⁷, John Marshall⁸, Claudia C Dos Santos⁹, Brent W Winston¹⁰, Asher A Mendelson¹¹, Chintan Dave¹², Lauralyn McIntyre^{1

13

14}

Affiliations

¹ Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
² Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
³ Regenerative Medicine Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁴ Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁵ Department of Cell and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
⁶ Department of Anesthesiology and Pain Medicine, University of Ottawa, The Ottawa Hospital, Ottawa, ON, Canada.
⁷ Department of Medicine, Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada.
⁸ Department of Surgery (Critical Care), University of Toronto, Toronto, ON, Canada.
⁹ Keenan Research Centre for Biomedical Science and Interdepartmental Division of Critical Care, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada.
¹¹ Section of Critical Care Medicine, Department of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
¹² Division of Critical Care Medicine, Department of Medicine, Western University, London, ON, Canada.
¹³ Department of Medicine (Division of Critical Care), University of Ottawa, Ottawa, ON, Canada.
¹⁴ Department of Medicine (Critical Care), The Ottawa Hospital, Ottawa Hospital Research Institute, Centre for Transfusion and Critical Care Research, Ottawa, ON, Canada.

Abstract

Background: In preclinical studies, mesenchymal stromal cells (MSCs), including umbilical cord-derived MSCs (UC-MSCs), demonstrate the ability to modulate numerous pathophysiological processes related to sepsis; however, a systematic synthesis of the literature is needed to assess the efficacy of UC-MSCs for treating sepsis.

Objective: To examine the effects of UC-MSCs on overall mortality (primary outcome) as well as on organ dysfunction, coagulopathy, endothelial permeability, pathogen clearance, and systemic inflammation (secondary outcomes) at prespecified time intervals in preclinical models of sepsis.

Methods: A systematic search was conducted on Embase, Ovid MEDLINE, and Web of Science up to June 20, 2023. Preclinical controlled studies using in vivo sepsis models with systemic UC-MSC administration were included. Meta-analyses were conducted and expressed as odds ratios (OR) and ratios of the weighted means with 95% CI for categorical and continuous data, respectively. Risk of bias was assessed with the SYRCLE tool.

Results: Twenty-six studies (34 experiments, n = 1258 animals) were included in this review. Overall mortality was significantly reduced with UC-MSC treatment as compared to controls (OR: 0.26, 95% CI: 0.18-0.36). At various prespecified time intervals, UC-MSCs reduced surrogate measures of organ dysfunction related to the kidney, liver, and lung; reduced coagulopathy and endothelial permeability; and enhanced pathogen clearance from multiple sites. UC-MSCs also modulated systemic inflammatory mediators. No studies were rated as low risk across all SYCLE domains.

Conclusions: These results demonstrate the efficacy of UC-MSC treatment in preclinical sepsis models and highlight their potential as a therapeutic intervention for septic shock.

Keywords: mesenchymal stromal (stem) cell; preclinical; sepsis; systematic review; umbilical cord.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Animals
Mesenchymal Stem Cell Transplantation* / adverse effects
Mesenchymal Stem Cell Transplantation* / methods
Mesenchymal Stem Cells* / physiology
Multiple Organ Failure
Sepsis* / therapy
Shock, Septic*
Umbilical Cord

Grants and funding

Stem Cell Network