Human liver stem cells and derived extracellular vesicles protect from sepsis-induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsis
Abstract Background Sepsis is a condition with high mortality and morbidity, characterized by deregulation of the immune response against the pathogen. Current treatment strategies rely mainly on antibiotics and supportive care. However, there is growing interest in exploring cell-based therapies as...
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SpringerOpen
2024-12-01
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| Series: | Intensive Care Medicine Experimental |
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| Online Access: | https://doi.org/10.1186/s40635-024-00701-z |
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| author | Andrea Costamagna Chiara Pasquino Sara Lamorte Victor Navarro-Tableros Luisa Delsedime Vito Fanelli Giovanni Camussi Lorenzo Del Sorbo |
| author_facet | Andrea Costamagna Chiara Pasquino Sara Lamorte Victor Navarro-Tableros Luisa Delsedime Vito Fanelli Giovanni Camussi Lorenzo Del Sorbo |
| author_sort | Andrea Costamagna |
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| description | Abstract Background Sepsis is a condition with high mortality and morbidity, characterized by deregulation of the immune response against the pathogen. Current treatment strategies rely mainly on antibiotics and supportive care. However, there is growing interest in exploring cell-based therapies as complementary approaches. Human liver stem cells (HLSCs) are pluripotent cells of mesenchymal origin, showing some advantages compared to mesenchymal stem cells in terms of immunomodulatory properties. HSLC-derived extracellular vesicles (EVs) exhibited a superior efficacy profile compared to cells due to their potential to get through biological barriers and possibly to avoid tumorigenicity and showed to be effective in vivo and ex vivo models of liver and kidney disease. The potential of HLSCs and their EVs in recovering damage to distal organs due to sepsis other than the kidney remains unknown. This study aimed to investigate the therapeutic potential of the intravenous administration of HSLCs or HSLCs-derived EVs in a murine model of sepsis. Results Sepsis was induced by caecal ligation and puncture (CLP) on C57/BL6 mice. After CLP, mice were assigned to receive either normal saline, HLSCs or their EVs and compared to a sham group which underwent only laparotomy. Survival, persistence of bacteraemia, lung function evaluation, histology and bone marrow analysis were performed. Administration of HLSCs or HLSC-EVs resulted in improved bacterial clearance and lung function in terms of lung elastance and oedema. Naïve murine hematopoietic progenitors in bone marrow were enhanced after treatment as well. Administration of HLSCs and HLSC-EVs after CLP to significantly improved survival. Conclusions Treatment with HLSCs or HLSC-derived EVs was effective in improving acute lung injury, dysmyelopoiesis and ultimately survival in this experimental murine model of lethal sepsis. |
| format | Article |
| id | doaj-art-c05cd6811354436fa5c1c3e4f09de01a |
| institution | Kabale University |
| issn | 2197-425X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Intensive Care Medicine Experimental |
| spelling | doaj-art-c05cd6811354436fa5c1c3e4f09de01a2024-12-08T12:06:56ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2024-12-0112111410.1186/s40635-024-00701-zHuman liver stem cells and derived extracellular vesicles protect from sepsis-induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsisAndrea Costamagna0Chiara Pasquino1Sara Lamorte2Victor Navarro-Tableros3Luisa Delsedime4Vito Fanelli5Giovanni Camussi6Lorenzo Del Sorbo7Department of Surgical Sciences, University of TurinMolecular Biotechnology Center, University of TurinPrincess Margaret Cancer Center, University Health Network2i3T – Scarl.-Molecular Biotechnology Center (MBC), University of TurinPathology Unit, A.O.U, Città Della Salute E Della Scienza Di TorinoDepartment of Surgical Sciences, University of TurinDepartment of Medical Sciences, University of TurinInterdepartmental Division of Critical Care Medicine, University Health Network, University of TorontoAbstract Background Sepsis is a condition with high mortality and morbidity, characterized by deregulation of the immune response against the pathogen. Current treatment strategies rely mainly on antibiotics and supportive care. However, there is growing interest in exploring cell-based therapies as complementary approaches. Human liver stem cells (HLSCs) are pluripotent cells of mesenchymal origin, showing some advantages compared to mesenchymal stem cells in terms of immunomodulatory properties. HSLC-derived extracellular vesicles (EVs) exhibited a superior efficacy profile compared to cells due to their potential to get through biological barriers and possibly to avoid tumorigenicity and showed to be effective in vivo and ex vivo models of liver and kidney disease. The potential of HLSCs and their EVs in recovering damage to distal organs due to sepsis other than the kidney remains unknown. This study aimed to investigate the therapeutic potential of the intravenous administration of HSLCs or HSLCs-derived EVs in a murine model of sepsis. Results Sepsis was induced by caecal ligation and puncture (CLP) on C57/BL6 mice. After CLP, mice were assigned to receive either normal saline, HLSCs or their EVs and compared to a sham group which underwent only laparotomy. Survival, persistence of bacteraemia, lung function evaluation, histology and bone marrow analysis were performed. Administration of HLSCs or HLSC-EVs resulted in improved bacterial clearance and lung function in terms of lung elastance and oedema. Naïve murine hematopoietic progenitors in bone marrow were enhanced after treatment as well. Administration of HLSCs and HLSC-EVs after CLP to significantly improved survival. Conclusions Treatment with HLSCs or HLSC-derived EVs was effective in improving acute lung injury, dysmyelopoiesis and ultimately survival in this experimental murine model of lethal sepsis.https://doi.org/10.1186/s40635-024-00701-zShockSepticMesenchymal stem cellsExtracellular vesiclesAcute lung injuryMyelopoiesis |
| spellingShingle | Andrea Costamagna Chiara Pasquino Sara Lamorte Victor Navarro-Tableros Luisa Delsedime Vito Fanelli Giovanni Camussi Lorenzo Del Sorbo Human liver stem cells and derived extracellular vesicles protect from sepsis-induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsis Intensive Care Medicine Experimental Shock Septic Mesenchymal stem cells Extracellular vesicles Acute lung injury Myelopoiesis |
| title | Human liver stem cells and derived extracellular vesicles protect from sepsis-induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsis |
| title_full | Human liver stem cells and derived extracellular vesicles protect from sepsis-induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsis |
| title_fullStr | Human liver stem cells and derived extracellular vesicles protect from sepsis-induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsis |
| title_full_unstemmed | Human liver stem cells and derived extracellular vesicles protect from sepsis-induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsis |
| title_short | Human liver stem cells and derived extracellular vesicles protect from sepsis-induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsis |
| title_sort | human liver stem cells and derived extracellular vesicles protect from sepsis induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsis |
| topic | Shock Septic Mesenchymal stem cells Extracellular vesicles Acute lung injury Myelopoiesis |
| url | https://doi.org/10.1186/s40635-024-00701-z |
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