scholarly journals Combined Therapy of Pegylated G-CSF and Alxn4100TPO Improves Survival and Mitigates Acute Radiation Syndrome after Whole-Body Ionizing Irradiation Alone and Followed by Wound Trauma

2017 ◽  
Vol 188 (5) ◽  
pp. 556-570 ◽  
Author(s):  
Juliann G. Kiang ◽  
Min Zhai ◽  
David L. Bolduc ◽  
Joan T. Smith ◽  
Marsha N. Anderson ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Acute Radiation ◽  
Whole Body ◽  
Ionizing Irradiation ◽  
Acute Radiation Syndrome

scholarly journals Mitigating Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on Hematopoietic Acute Radiation Syndrome after Total-Body Ionizing Irradiation in Mice

2019 ◽  
Vol 192 (6) ◽  
pp. 602 ◽  
Author(s):  
Yong-Jae Kim ◽  
Jinseon Jeong ◽  
Su-Hyun Shin ◽  
Do Young Lee ◽  
Ki-Young Sohn ◽  
...  
Keyword(s):  
Acute Radiation ◽  
Ionizing Irradiation ◽  
Acute Radiation Syndrome ◽  
Total Body

scholarly journals Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome.

2020 ◽  
Author(s):  
Alison Accarie ◽  
Bruno L'homme ◽  
Mohamedamine Benadjaoud ◽  
Sai Kiang Lim ◽  
Chadan Guha ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Intestinal Epithelium ◽  
Stromal Cells ◽  
Acute Radiation ◽  
Whole Body ◽  
Mucosal Barrier ◽  
Acute Radiation Syndrome ◽  
Radiation Induced ◽  
Small Intestinal

Abstract Background: Human exposure to high doses of radiation resulting in acute radiation syndrome and death can rapidly escalate to a mass casualty catastrophe in the event of nuclear accidents or terrorism. The primary reason is that there is presently no effective treatment option, especially for radiation-induced gastrointestinal syndrome. This syndrome results from disruption of mucosal barrier integrity leading to severe dehydration, blood loss and sepsis. In this study, we tested whether extracellular vesicles derived from mesenchymal stromal cells (MSC) could reduce radiation-related mucosal barrier damage and reduce radiation-induced animal mortality. Methods: Human MSC-derived extracellular vesicles were intravenously administered to NUDE mice, 3, 24 and 48 hours after lethal whole-body irradiation (10 Grays). Integrity of the small intestine epithelial barrier was assessed by morphologic analysis, immunostaining for tight junction protein (claudin-3) and in vivo permeability to 4 kDa FITC-labeled dextran. Renewal of the small intestinal epithelium was determined by quantifying epithelial cell apoptosis (TUNEL staining) and proliferation (Ki67 immunostaining). Statistical analyses were performed using one-way ANOVA followed by a Tukey test. Statistical analyses of mouse survival were performed using Kaplan-Meier and Cox methods. Results: We demonstrated that MSC-derived extracellular vesicles treatment reduced by 85% the instantaneous mortality risk in mice subjected to 10 Grays whole-body irradiation and so increased their survival time. This effect could be attributed to the efficacy of MSC-derived extracellular vesicles in reducing mucosal barrier disruption. We showed that the MSC-derived extracellular vesicles improved the renewal of the small intestinal epithelium by stimulating proliferation and inhibiting apoptosis of the epithelial crypt cells. The MSC-derived extracellular vesicles also reduced radiation-induced mucosal permeability as evidenced by the preservation of claudin-3 immunostaining at the tight junctions of the epithelium.Conclusions: MSC-derived extracellular vesicles promote epithelial repair and regeneration and preserve structural integrity of the intestinal epithelium in mice exposed to radiation-induced gastrointestinal toxicity. Our results suggest that the administration of MSC-derived extracellular vesicles could be an effective therapy for limiting acute radiation syndrome.

scholarly journals Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome.

2020 ◽  
Author(s):  
Alison Accarie ◽  
Bruno L'homme ◽  
Mohamedamine Benadjaoud ◽  
Sai Kiang Lim ◽  
Chadan Guha ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Intestinal Epithelium ◽  
Stromal Cells ◽  
Acute Radiation ◽  
Whole Body ◽  
Mucosal Barrier ◽  
Acute Radiation Syndrome ◽  
Radiation Induced ◽  
Small Intestinal

Abstract Background: Human exposure to high doses of radiation resulting in acute radiation syndrome and death can rapidly escalate to a mass casualty catastrophe in the event of nuclear accidents or terrorism. The primary reason is that there is presently no effective treatment option, especially for radiation-induced gastrointestinal syndrome. This syndrome results from disruption of mucosal barrier integrity leading to severe dehydration, blood loss and sepsis. In this study, we tested whether extracellular vesicles derived from mesenchymal stromal cells (MSC) could reduce radiation-related mucosal barrier damage and reduce radiation-induced animal mortality. Methods: HumanMSC-derived extracellular vesicles were intravenously administered to NUDE mice, 3, 24 and 48 hours after lethal whole-body irradiation (10 Grays). Integrity of the small intestine epithelial barrier was assessed by morphologic analysis, immunostaining for tight junction protein (claudin-3) and in vivo permeability to 4 kDa FITC-labeled dextran. Renewal of the small intestinal epithelium was determined by quantifying epithelial cell apoptosis (TUNEL staining) and proliferation (Ki67 immunostaining). Statistical analyses were performed using one-way ANOVA followed by a Tukey test. Statistical analyses of mouse survival were performed using Kaplan-Meier and Cox methods. Results: We demonstrated that MSC-derived extracellular vesicles treatment reduced by 85% the instantaneous mortality risk in mice subjected to 10 Grays whole-body irradiation and so increased their survival time. This effect could be attributed to the efficacy of MSC-derived extracellular vesicles in reducing mucosal barrier disruption. We showed that the MSC-derived extracellular vesicles improved the renewal of the small intestinal epithelium by stimulating proliferation and inhibiting apoptosis of the epithelial crypt cells. The MSC-derived extracellular vesicles also reduced radiation-induced mucosal permeability as evidenced by the preservation of claudin-3 immunostaining at the tight junctions of the epithelium. Conclusions: MSC-derived extracellular vesicles promote epithelial repair and regeneration and preserve structural integrity of the intestinal epithelium in mice exposed to radiation-induced gastrointestinal toxicity. Our results suggest that the administration of MSC-derived extracellular vesicles could be an effective therapy for limiting acute radiation syndrome.

scholarly journals Small extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome.

2020 ◽  
Author(s):  
Alison Accarie ◽  
Bruno L'homme ◽  
Mohamedamine Benadjaoud ◽  
Sai Kiang Lim ◽  
Chadan Guha ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Intestinal Epithelium ◽  
Stromal Cells ◽  
Acute Radiation ◽  
Whole Body ◽  
Mucosal Barrier ◽  
Acute Radiation Syndrome ◽  
Radiation Induced ◽  
Small Intestinal

Abstract Background: Human exposure to high doses of radiation resulting in acute radiation syndrome and death could rapidly escalate to a mass casualty catastrophe in the event of nuclear accidents or terrorism. The primary reason is that there is presently no effective treatment option, especially for radiation-induced gastrointestinal syndrome. This syndrome results from disruption of mucosal barrier integrity leading to severe dehydration, blood loss and sepsis. In this study, we tested whether small extracellular vesicles/exosomes derived from mesenchymal stromal cells (MSC) could reduce radiation-related mucosal barrier damage and reduce radiation-induced animal mortality. Methods: Human MSC-derived small extracellular vesicles/exosomes were intravenously administered to NUDE mice, 3, 24 and 48 hours after lethal whole-body irradiation (10 Gy). Integrity of the small intestine epithelial barrier was assessed by morphologic analysis, immunostaining for tight junction protein (claudin-3) and in vivo permeability to 4 kDa FITC-labeled dextran. Renewal of small intestinal epithelium was determined by the quantification of epithelial cell apoptosis (TUNEL staining) and proliferation (Ki67 immunostaining). Statistical analyses were performed using one-way ANOVA followed by a Tukey test. Statistical analyses of mouse survival were performed using the methods of Kaplan-Meier and Cox. Results: We demonstrated that MSC-derived small extracellular vesicles/exosomes treatment reduced by 85% the instantaneous mortality risk in mice subjected to 10 Gy whole-body irradiation and thus increased their survival time. This effect could be attributed to the efficacy of MSC-derived small extracellular vesicles/exosomes in reducing mucosal barrier disruption. We showed that MSC-derived small extracellular vesicles/exosomes improved renewal of the small intestinal epithelium by stimulating proliferation and inhibiting apoptosis of the epithelial crypt cells. MSC-derived small extracellular vesicles/exosomes also reduced radiation-induced mucosal permeability as evidenced by the preservation of claudin-3 immunostaining at the tight junctions of the epithelium. Conclusions: MSC-derived small extracellular vesicles/exosomes promote epithelial repair and regeneration and preserve structural integrity of the intestinal epithelium in mice exposed to radiation-induced gastrointestinal toxicity. Our results suggest that the administration of MSC-derived small extracellular vesicles/exosomes could be a treatment modality to limit acute radiation syndrome.

scholarly journals Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome.

2020 ◽  
Author(s):  
Alison Accarie ◽  
Bruno L'homme ◽  
Mohamedamine Benadjaoud ◽  
Sai Kiang Lim ◽  
Chadan Guha ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Intestinal Epithelium ◽  
Stromal Cells ◽  
Acute Radiation ◽  
Whole Body ◽  
Mucosal Barrier ◽  
Acute Radiation Syndrome ◽  
Radiation Induced ◽  
Small Intestinal

Abstract Background: Human exposure to high doses of radiation resulting in acute radiation syndrome and death can rapidly escalate to a mass casualty catastrophe in the event of nuclear accidents or terrorism. The primary reason is that there is presently no effective treatment option, especially for radiation-induced gastrointestinal syndrome. This syndrome results from disruption of mucosal barrier integrity leading to severe dehydration, blood loss and sepsis. In this study, we tested whether extracellular vesicles derived from mesenchymal stromal cells (MSC) could reduce radiation-related mucosal barrier damage and reduce radiation-induced animal mortality. Methods: Human MSC-derived extracellular vesicles were intravenously administered to NUDE mice, 3, 24 and 48 hours after lethal whole-body irradiation (10 Grays). Integrity of the small intestine epithelial barrier was assessed by morphologic analysis, immunostaining for tight junction protein (claudin-3) and in vivo permeability to 4 kDa FITC-labeled dextran. Renewal of the small intestinal epithelium was determined by quantifying epithelial cell apoptosis (TUNEL staining) and proliferation (Ki67 immunostaining). Statistical analyses were performed using one-way ANOVA followed by a Tukey test. Statistical analyses of mouse survival were performed using Kaplan-Meier and Cox methods. Results: We demonstrated that MSC-derived extracellular vesicles treatment reduced by 85% the instantaneous mortality risk in mice subjected to 10 Grays whole-body irradiation and so increased their survival time. This effect could be attributed to the efficacy of MSC-derived extracellular vesicles in reducing mucosal barrier disruption. We showed that the MSC-derived extracellular vesicles improved the renewal of the small intestinal epithelium by stimulating proliferation and inhibiting apoptosis of the epithelial crypt cells. The MSC-derived extracellular vesicles also reduced radiation-induced mucosal permeability as evidenced by the preservation of claudin-3 immunostaining at the tight junctions of the epithelium. Conclusions: MSC-derived extracellular vesicles promote epithelial repair and regeneration and preserve structural integrity of the intestinal epithelium in mice exposed to radiation-induced gastrointestinal toxicity. Our results suggest that the administration of MSC-derived extracellular vesicles could be an effective therapy for limiting acute radiation syndrome.

scholarly journals Long-Term Hematopoietic Stem Cell Damage in a Murine Model of the Hematopoietic Syndrome of the Acute Radiation Syndrome

2012 ◽  
Vol 103 (4) ◽  
pp. 356-366 ◽  
Author(s):  
Hui Lin Chua ◽  
P. Artur Plett ◽  
Carol H. Sampson ◽  
Mandar Joshi ◽  
Rebeka Tabbey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Murine Model ◽  
Cell Damage ◽  
Acute Radiation ◽  
Hematopoietic Stem ◽  
Acute Radiation Syndrome

The Acute Gastrointestinal Subsyndrome of the Acute Radiation Syndrome

2012 ◽  
Vol 103 (4) ◽  
pp. 411-426 ◽  
Author(s):  
Thomas J. MacVittie ◽  
Ann M. Farese ◽  
Alexander Bennett ◽  
Daniel Gelfond ◽  
Terez Shea-Donohue ◽  
...  
Keyword(s):  
Acute Radiation ◽  
Acute Radiation Syndrome
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