Mesenchymal Stem Cell Extracellular Vesicles Mitigate Vascular Permeability and Injury in the Small Intestine and Lung in a Mouse Model of Hemorrhagic Shock and Trauma
| Autor: | Mark Barry, Alpa Trivedi, Praneeti Pathipati, Byron Y. Miyazawa, Lindsay R. Vivona, Padma Priya Togarrati, Manisha Khakoo, Heather Tanner, Philip Norris, Shibani Pati |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Physical Injury - Accidents and Adverse Effects
Clinical Sciences Nursing Cardiorespiratory Medicine and Haematology Shock Hemorrhagic Critical Care and Intensive Care Medicine Small Regenerative Medicine Article Capillary Permeability Extracellular Vesicles Mice Intestine Small 2.1 Biological and endogenous factors Animals Humans Aetiology Hemorrhagic Lung vascular permeability mesenchymal stem cells Animal Shock Mesenchymal Stem Cells Hydrogen Peroxide Lung Injury gut and lung injury Stem Cell Research Emergency & Critical Care Medicine Intestine Disease Models Animal Hemorrhagic shock Disease Models Surgery Stem Cell Research - Nonembryonic - Non-Human Caco-2 Cells |
| Zdroj: | J Trauma Acute Care Surg The journal of trauma and acute care surgery, vol 92, iss 3 |
| Popis: | BackgroundHemorrhagic shock and trauma (HS/T)-induced gut injury may play a critical role in the development of multi-organ failure. Novel therapies that target gut injury and vascular permeability early after HS/T could have substantial impacts on trauma patients. In this study, we investigate the therapeutic potential of human mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC EVs) in vivo in HS/T in mice and in vitro in Caco-2 human intestinal epithelial cells.MethodsIn vivo, using a mouse model of HS/T, vascular permeability to a 10-kDa dextran dye and histopathologic injury in the small intestine and lungs were measured among mice. Groups were (1) sham, (2) HS/T + lactated Ringer's (LR), (3) HS/T + MSCs, and (4) HS/T + MSC EVs. In vitro, Caco-2 cell monolayer integrity was evaluated by an epithelial cell impedance assay. Caco-2 cells were pretreated with control media, MSC conditioned media (CM), or MSC EVs, then challenged with hydrogen peroxide (H2O2).ResultsIn vivo, both MSCs and MSC EVs significantly reduced vascular permeability in the small intestine (fluorescence units: sham, 456 ± 88; LR, 1067 ± 295; MSC, 765 ± 258; MSC EV, 715 ± 200) and lung (sham, 297 ± 155; LR, 791 ± 331; MSC, 331 ± 172; MSC EV, 303 ± 88). Histopathologic injury in the small intestine and lung was also attenuated by MSCs and MSC EVs. In vitro, MSC CM but not MSC EVs attenuated the increased permeability among Caco-2 cell monolayers challenged with H2O2.ConclusionMesenchymal stem cell EVs recapitulate the effects of MSCs in reducing vascular permeability and injury in the small intestine and lungs in vivo, suggesting MSC EVs may be a potential cell-free therapy targeting multi-organ dysfunction in HS/T. This is the first study to demonstrate that MSC EVs improve both gut and lung injury in an animal model of HS/T. |
| Databáze: | OpenAIRE |
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