Role of tissue factor in the procoagulant and antibacterial effects of human adipose-derived mesenchymal stem cells during pneumosepsis in mice
Abstract Background Adult mesenchymal stem cells (MSCs) improve the host response during experimental sepsis in animals. MSCs from various sources express a procoagulant activity that has been linked to the expression of tissue factor. This study sought to determine the role of tissue factor associa...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1391-x |
| _version_ | 1819111457834401792 |
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| author | Desirée Perlee Alex F. de Vos Brendon P. Scicluna Anja Maag Pablo Mancheño Olga de la Rosa Wilfried Dalemans Sandrine Florquin Cornelis van’t Veer Eleuterio Lombardo Tom van der Poll |
| author_facet | Desirée Perlee Alex F. de Vos Brendon P. Scicluna Anja Maag Pablo Mancheño Olga de la Rosa Wilfried Dalemans Sandrine Florquin Cornelis van’t Veer Eleuterio Lombardo Tom van der Poll |
| author_sort | Desirée Perlee |
| collection | DOAJ |
| description | Abstract Background Adult mesenchymal stem cells (MSCs) improve the host response during experimental sepsis in animals. MSCs from various sources express a procoagulant activity that has been linked to the expression of tissue factor. This study sought to determine the role of tissue factor associated with adipose-derived MSCs (ASCs) in their procoagulant and antibacterial effects during pneumonia-derived sepsis. Methods Mice were infused intravenously with ASCs or vehicle after infection with the common human pathogen Klebsiella pneumoniae via the airways. Results Infusion of freshly cultured or cryopreserved ASCs induced the expression of many genes associated with tissue factor signaling and coagulation activation in the lungs. Freshly cultured and cryopreserved ASCs, as well as ASC lysates, exerted procoagulant activity in vitro as determined by a fibrin generation assay, which was almost completely inhibited by an anti-tissue factor antibody. Infusion of cryopreserved ASCs was associated with a rise in plasma thrombin-antithrombin complexes (indicative of coagulation activation) and formation of multiple thrombi in the lungs 4 h post-infusion. Preincubation of ASCs with anti-tissue factor antibody prior to infusion prevented the rise in plasma thrombin-antithrombin complex concentrations but did not influence thrombus formation in the lungs. ASCs reduced bacterial loads in the lungs and liver at 48 h after infection, which was not influenced by preincubation with anti-tissue factor antibody. At this late time point, microthrombi in the lungs were not detected anymore. Conclusion These data indicate that ASC-associated tissue factor is responsible for systemic activation of coagulation after infusion of ASCs but not for the formation of microthrombi in the lungs or antibacterial effects. |
| first_indexed | 2024-12-22T03:57:55Z |
| format | Article |
| id | doaj.art-9ae00b646c894373ae7289ae8e6bde7c |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-22T03:57:55Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-9ae00b646c894373ae7289ae8e6bde7c2022-12-21T18:39:49ZengBMCStem Cell Research & Therapy1757-65122019-09-011011910.1186/s13287-019-1391-xRole of tissue factor in the procoagulant and antibacterial effects of human adipose-derived mesenchymal stem cells during pneumosepsis in miceDesirée Perlee0Alex F. de Vos1Brendon P. Scicluna2Anja Maag3Pablo Mancheño4Olga de la Rosa5Wilfried Dalemans6Sandrine Florquin7Cornelis van’t Veer8Eleuterio Lombardo9Tom van der Poll10Center of Experimental & Molecular Medicine, Amsterdam University Medical Centers, University of AmsterdamCenter of Experimental & Molecular Medicine, Amsterdam University Medical Centers, University of AmsterdamCenter of Experimental & Molecular Medicine, Amsterdam University Medical Centers, University of AmsterdamCenter of Experimental & Molecular Medicine, Amsterdam University Medical Centers, University of AmsterdamTiGenix SAUTiGenix SAUTiGenix NVDepartment of Pathology, Amsterdam University Medical Centers, University of AmsterdamCenter of Experimental & Molecular Medicine, Amsterdam University Medical Centers, University of AmsterdamTiGenix SAUCenter of Experimental & Molecular Medicine, Amsterdam University Medical Centers, University of AmsterdamAbstract Background Adult mesenchymal stem cells (MSCs) improve the host response during experimental sepsis in animals. MSCs from various sources express a procoagulant activity that has been linked to the expression of tissue factor. This study sought to determine the role of tissue factor associated with adipose-derived MSCs (ASCs) in their procoagulant and antibacterial effects during pneumonia-derived sepsis. Methods Mice were infused intravenously with ASCs or vehicle after infection with the common human pathogen Klebsiella pneumoniae via the airways. Results Infusion of freshly cultured or cryopreserved ASCs induced the expression of many genes associated with tissue factor signaling and coagulation activation in the lungs. Freshly cultured and cryopreserved ASCs, as well as ASC lysates, exerted procoagulant activity in vitro as determined by a fibrin generation assay, which was almost completely inhibited by an anti-tissue factor antibody. Infusion of cryopreserved ASCs was associated with a rise in plasma thrombin-antithrombin complexes (indicative of coagulation activation) and formation of multiple thrombi in the lungs 4 h post-infusion. Preincubation of ASCs with anti-tissue factor antibody prior to infusion prevented the rise in plasma thrombin-antithrombin complex concentrations but did not influence thrombus formation in the lungs. ASCs reduced bacterial loads in the lungs and liver at 48 h after infection, which was not influenced by preincubation with anti-tissue factor antibody. At this late time point, microthrombi in the lungs were not detected anymore. Conclusion These data indicate that ASC-associated tissue factor is responsible for systemic activation of coagulation after infusion of ASCs but not for the formation of microthrombi in the lungs or antibacterial effects.http://link.springer.com/article/10.1186/s13287-019-1391-xSepsisMesenchymal stem cellsImmunomodulationCoagulation |
| spellingShingle | Desirée Perlee Alex F. de Vos Brendon P. Scicluna Anja Maag Pablo Mancheño Olga de la Rosa Wilfried Dalemans Sandrine Florquin Cornelis van’t Veer Eleuterio Lombardo Tom van der Poll Role of tissue factor in the procoagulant and antibacterial effects of human adipose-derived mesenchymal stem cells during pneumosepsis in mice Stem Cell Research & Therapy Sepsis Mesenchymal stem cells Immunomodulation Coagulation |
| title | Role of tissue factor in the procoagulant and antibacterial effects of human adipose-derived mesenchymal stem cells during pneumosepsis in mice |
| title_full | Role of tissue factor in the procoagulant and antibacterial effects of human adipose-derived mesenchymal stem cells during pneumosepsis in mice |
| title_fullStr | Role of tissue factor in the procoagulant and antibacterial effects of human adipose-derived mesenchymal stem cells during pneumosepsis in mice |
| title_full_unstemmed | Role of tissue factor in the procoagulant and antibacterial effects of human adipose-derived mesenchymal stem cells during pneumosepsis in mice |
| title_short | Role of tissue factor in the procoagulant and antibacterial effects of human adipose-derived mesenchymal stem cells during pneumosepsis in mice |
| title_sort | role of tissue factor in the procoagulant and antibacterial effects of human adipose derived mesenchymal stem cells during pneumosepsis in mice |
| topic | Sepsis Mesenchymal stem cells Immunomodulation Coagulation |
| url | http://link.springer.com/article/10.1186/s13287-019-1391-x |
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