Evaluation of Mesenchymal Stem Cell Therapy for Sepsis: A Randomized Controlled Porcine Study
Background: Treatment with mesenchymal stem cells (MSCs) has elicited considerable interest as an adjunctive therapy in sepsis. However, the encouraging effects of experiments with MSC in rodents have not been adequately studied in large-animal models with better relevance to human sepsis.Objectives...
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Frontiers Media S.A.
2020-02-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00126/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jan Horak Jan Horak Lukas Nalos Lukas Nalos Vendula Martinkova Vendula Martinkova Vaclav Tegl Vaclav Tegl Lucie Vistejnova Lucie Vistejnova Jitka Kuncova Jitka Kuncova Michaela Kohoutova Michaela Kohoutova Dagmar Jarkovska Dagmar Jarkovska Martina Dolejsova Jan Benes Jan Benes Milan Stengl Milan Stengl Martin Matejovic Martin Matejovic |
spellingShingle |
Jan Horak Jan Horak Lukas Nalos Lukas Nalos Vendula Martinkova Vendula Martinkova Vaclav Tegl Vaclav Tegl Lucie Vistejnova Lucie Vistejnova Jitka Kuncova Jitka Kuncova Michaela Kohoutova Michaela Kohoutova Dagmar Jarkovska Dagmar Jarkovska Martina Dolejsova Jan Benes Jan Benes Milan Stengl Milan Stengl Martin Matejovic Martin Matejovic Evaluation of Mesenchymal Stem Cell Therapy for Sepsis: A Randomized Controlled Porcine Study Frontiers in Immunology sepsis septic shock acute organ dysfunction mesenchymal stem cells cell therapy immunomodulation |
author_facet |
Jan Horak Jan Horak Lukas Nalos Lukas Nalos Vendula Martinkova Vendula Martinkova Vaclav Tegl Vaclav Tegl Lucie Vistejnova Lucie Vistejnova Jitka Kuncova Jitka Kuncova Michaela Kohoutova Michaela Kohoutova Dagmar Jarkovska Dagmar Jarkovska Martina Dolejsova Jan Benes Jan Benes Milan Stengl Milan Stengl Martin Matejovic Martin Matejovic |
author_sort |
Jan Horak |
title |
Evaluation of Mesenchymal Stem Cell Therapy for Sepsis: A Randomized Controlled Porcine Study |
title_short |
Evaluation of Mesenchymal Stem Cell Therapy for Sepsis: A Randomized Controlled Porcine Study |
title_full |
Evaluation of Mesenchymal Stem Cell Therapy for Sepsis: A Randomized Controlled Porcine Study |
title_fullStr |
Evaluation of Mesenchymal Stem Cell Therapy for Sepsis: A Randomized Controlled Porcine Study |
title_full_unstemmed |
Evaluation of Mesenchymal Stem Cell Therapy for Sepsis: A Randomized Controlled Porcine Study |
title_sort |
evaluation of mesenchymal stem cell therapy for sepsis: a randomized controlled porcine study |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-02-01 |
description |
Background: Treatment with mesenchymal stem cells (MSCs) has elicited considerable interest as an adjunctive therapy in sepsis. However, the encouraging effects of experiments with MSC in rodents have not been adequately studied in large-animal models with better relevance to human sepsis.Objectives: Here, we aimed to assess safety and efficacy of bone marrow-derived MSCs in a clinically relevant porcine model of progressive peritonitis-induced sepsis.Methods: Thirty-two anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned into four groups (n = 8 per group): (1) sham-operated group (CONTROL); (2) sham-operated group treated with MSCs (MSC-CONTROL); (3) sepsis group with standard supportive care (SEPSIS); and (4) sepsis group treated with MSCs (MSC-SEPSIS). Peritoneal sepsis was induced by inoculating cultivated autologous feces. MSCs (1 × 106/kg) were administered intravenously at 6 h after sepsis induction.Results: Before, 12, 18, and 24 h after the induction of peritonitis, we measured systemic, regional, and microvascular hemodynamics, multiple-organ functions, mitochondrial energy metabolism, systemic immune-inflammatory response, and oxidative stress. Administration of MSCs in the MSC-CONTROL group did not elicit any measurable acute effects. Treatment of septic animals with MSCs failed to mitigate sepsis-induced hemodynamic alterations or the gradual rise in Sepsis-related organ failure assessment scores. MSCs did not confer any protection against sepsis-mediated cellular myocardial depression and mitochondrial dysfunction. MSCs also failed to modulate the deregulated immune-inflammatory response.Conclusion: Intravenous administration of bone marrow-derived MSCs to healthy animals was well-tolerated. However, in this large-animal, clinically relevant peritonitis-induced sepsis model, MSCs were not capable of reversing any of the sepsis-induced disturbances in multiple biological, organ, and cellular systems. |
topic |
sepsis septic shock acute organ dysfunction mesenchymal stem cells cell therapy immunomodulation |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.00126/full |
work_keys_str_mv |
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doaj-20a0836abf8d4d94aa34c6545fa7c4942020-11-25T02:39:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011110.3389/fimmu.2020.00126473823Evaluation of Mesenchymal Stem Cell Therapy for Sepsis: A Randomized Controlled Porcine StudyJan Horak0Jan Horak1Lukas Nalos2Lukas Nalos3Vendula Martinkova4Vendula Martinkova5Vaclav Tegl6Vaclav Tegl7Lucie Vistejnova8Lucie Vistejnova9Jitka Kuncova10Jitka Kuncova11Michaela Kohoutova12Michaela Kohoutova13Dagmar Jarkovska14Dagmar Jarkovska15Martina Dolejsova16Jan Benes17Jan Benes18Milan Stengl19Milan Stengl20Martin Matejovic21Martin Matejovic22First Medical Department, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaDepartment of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaThird Department of Surgery, University Hospital Motol and First Medical School, Charles University, Prague, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaDepartment of Anesthesia and Intensive Care Medicine, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaDepartment of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaDepartment of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaDepartment of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaDepartment of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaDepartment of Anesthesia and Intensive Care Medicine, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaDepartment of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaFirst Medical Department, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaFaculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, CzechiaBackground: Treatment with mesenchymal stem cells (MSCs) has elicited considerable interest as an adjunctive therapy in sepsis. However, the encouraging effects of experiments with MSC in rodents have not been adequately studied in large-animal models with better relevance to human sepsis.Objectives: Here, we aimed to assess safety and efficacy of bone marrow-derived MSCs in a clinically relevant porcine model of progressive peritonitis-induced sepsis.Methods: Thirty-two anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned into four groups (n = 8 per group): (1) sham-operated group (CONTROL); (2) sham-operated group treated with MSCs (MSC-CONTROL); (3) sepsis group with standard supportive care (SEPSIS); and (4) sepsis group treated with MSCs (MSC-SEPSIS). Peritoneal sepsis was induced by inoculating cultivated autologous feces. MSCs (1 × 106/kg) were administered intravenously at 6 h after sepsis induction.Results: Before, 12, 18, and 24 h after the induction of peritonitis, we measured systemic, regional, and microvascular hemodynamics, multiple-organ functions, mitochondrial energy metabolism, systemic immune-inflammatory response, and oxidative stress. Administration of MSCs in the MSC-CONTROL group did not elicit any measurable acute effects. Treatment of septic animals with MSCs failed to mitigate sepsis-induced hemodynamic alterations or the gradual rise in Sepsis-related organ failure assessment scores. MSCs did not confer any protection against sepsis-mediated cellular myocardial depression and mitochondrial dysfunction. MSCs also failed to modulate the deregulated immune-inflammatory response.Conclusion: Intravenous administration of bone marrow-derived MSCs to healthy animals was well-tolerated. However, in this large-animal, clinically relevant peritonitis-induced sepsis model, MSCs were not capable of reversing any of the sepsis-induced disturbances in multiple biological, organ, and cellular systems.https://www.frontiersin.org/article/10.3389/fimmu.2020.00126/fullsepsisseptic shockacute organ dysfunctionmesenchymal stem cellscell therapyimmunomodulation |