[en] Mesenchymal stem cells (MSC) have immune regulatory properties that may ameliorate pathophysiological processes in sepsis. We determined the effect of allogeneic adipose-derived MSCs (Cx611) on the host response during sepsis due to community-acquired bacterial pneumonia (CABP) by measuring 29 plasma biomarkers and blood transcriptomes at six time points in 82 patients randomised to two intravenous infusions of Cx611 or placebo. Cx611 treatment enhanced several endothelial cell and procoagulant response plasma biomarkers, and led to increased expression of pathways related to innate immunity, haemostasis and apoptosis. Cx611 infusion in sepsis due to CABP is associated with broad host response alterations.
Disciplines :
Anesthesia & intensive care
Author, co-author :
Reijnders, Tom D Y ; Center for Experimental and Molecular Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands t.d.reijnders@amsterdamumc.nl
Laterre, Pierre-François; Department of Intensive Care Medicine, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
François, Bruno; Intensive care unit and Inserm CIC 1435 & UMR 1092, University Hospital Centre of Limoges, Limoges, France
Sánchez García, Miguel; Critical Care Department, San Carlos Clinic Hospital, Madrid, Spain
van Engelen, Tjitske S R; Center for Experimental and Molecular Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
Sie, Daoud; Department of Human Genetics, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Scicluna, Brendon P; Center for Experimental and Molecular Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands ; Center for Molecular Medicine and Biobanking, University of Malta, Msida, Malta ; Department of Applied Biomedical Science, University of Malta, Msida, Malta
Galinsky, Kevin J; Translational Biomarker Research, Takeda Pharmaceuticals, Cambridge, Massachusetts, USA
Butler, Joe M; Center for Experimental and Molecular Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
Lombardo, Eleuterio; Takeda Madrid Cell Therapy Technology Center, Tres Cantos, Spain
van der Poll, Tom ; Center for Experimental and Molecular Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands ; Division of Infectious Diseases, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
H2020 - 681031 - SEPCELL - Title of Proposal: Restoring the immune system homeostasis and organ function in severe community acquired pneumonia- induced sepsis through adipose derived allogeneic stem cells (SEPCELL Proje
Funders :
EU - European Union NWO - Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Funding text :
We thank Desir\u00E9e Perlee, PhD, for her role in the initial phases of the biomarker studies. We thank Augustijn M Klarenbeek, Jacky de Leeuw, Fayola de Lange, Barbara Dierdorp, and Tamara Dekker and the Amsterdam UMC Core Facility Genomics for their invaluable support in the laboratory and for providing HPC Genomics as high-performance compute resource. The SEPCELL study consortium is coordinated by Takeda Pharmaceuticals. The authors acknowledge the valued contribution of the investigators to the SEPCELL study. This study was supported by a grant from the European Union\u2019s Horizon 2020 Research and Innovation Program (agreement number 681031) and sponsored by TiGenix SAU (a wholly owned subsidiary of Takeda Pharmaceuticals). TDYR is supported by the research programme\u2019NACTAR\u2019, project\u2019MDR-phage\u2019 (grant number 16447), which is financed by the Dutch Research Council (NWO).This study was supported by a grant from the European Union\u2019s Horizon 2020 Research and Innovation Program (agreement number 681031) and sponsored by TiGenix SAU (a wholly owned subsidiary of Takeda Pharmaceuticals). TDYR is supported by the research programme 'NACTAR', project \u2018MDR-phage\u2019 (grant number 16447), which is financed by the Dutch Research Council (NWO).
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