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Regulation of vascular endothelial integrity by mesenchymal stem cell extracellular vesicles after hemorrhagic shock and trauma.
- Source :
-
Journal of translational medicine [J Transl Med] 2024 Jun 21; Vol. 22 (1), pp. 588. Date of Electronic Publication: 2024 Jun 21. - Publication Year :
- 2024
-
Abstract
- Background: Patients with hemorrhagic shock and trauma (HS/T) are vulnerable to the endotheliopathy of trauma (EOT), characterized by vascular barrier dysfunction, inflammation, and coagulopathy. Cellular therapies such as mesenchymal stem cells (MSCs) and MSC extracellular vesicles (EVs) have been proposed as potential therapies targeting the EOT. In this study we investigated the effects of MSCs and MSC EVs on endothelial and epithelial barrier integrity in vitro and in vivo in a mouse model of HS/T. This study addresses the systemic effects of HS/T on multiorgan EOT.<br />Methods: In vitro, pulmonary endothelial cell (PEC) and Caco-2 intestinal epithelial cell monolayers were treated with control media, MSC conditioned media (CM), or MSC EVs in varying doses and subjected to a thrombin or hydrogen peroxide (H <subscript>2</subscript> O <subscript>2</subscript> ) challenge, respectively. Monolayer permeability was evaluated with a cell impedance assay, and intercellular junction integrity was evaluated with immunofluorescent staining. In vivo, a mouse model of HS/T was used to evaluate the effects of lactated Ringer's (LR), MSCs, and MSC EVs on endothelial and epithelial intercellular junctions in the lung and small intestine as well as on plasma inflammatory biomarkers.<br />Results: MSC EVs and MSC CM attenuated permeability and preserved intercellular junctions of the PEC monolayer in vitro, whereas only MSC CM was protective of the Caco-2 epithelial monolayer. In vivo, both MSC EVs and MSCs mitigated the loss of endothelial adherens junctions in the lung and small intestine, though only MSCs had a protective effect on epithelial tight junctions in the lung. Several plasma biomarkers including MMP8 and VEGF were elevated in LR- and EV-treated but not MSC-treated mice.<br />Conclusions: In conclusion, MSC EVs could be a potential cell-free therapy targeting endotheliopathy after HS/T via preservation of the vascular endothelial barrier in multiple organs early after injury. Further research is needed to better understand the immunomodulatory effects of these products following HS/T and to move toward translating these therapies into clinical studies.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Humans
Caco-2 Cells
Endothelium, Vascular metabolism
Endothelium, Vascular pathology
Male
Wounds and Injuries pathology
Culture Media, Conditioned pharmacology
Mice
Endothelial Cells metabolism
Lung pathology
Hydrogen Peroxide metabolism
Intercellular Junctions metabolism
Extracellular Vesicles metabolism
Shock, Hemorrhagic metabolism
Mesenchymal Stem Cells metabolism
Mesenchymal Stem Cells cytology
Mice, Inbred C57BL
Subjects
Details
- Language :
- English
- ISSN :
- 1479-5876
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38907252
- Full Text :
- https://doi.org/10.1186/s12967-024-05406-1