Administration of Human MSC-Derived Extracellular Vesicles for the Treatment of Primary Sclerosing Cholangitis: Preclinical Data in MDR2 Knockout Mice.

Angioni, Roberta, Calì, Bianca, Vigneswara, Vasanthy, Crescenzi, Marika, Merino, Ana, Sánchez-Rodríguez, Ricardo, Liboni, Cristina, Hoogduijn, Martin J, Newsome, Philip Noel, Muraca, Maurizio, Russo, Francesco Paolo and Viola, Antonella (2020) Administration of Human MSC-Derived Extracellular Vesicles for the Treatment of Primary Sclerosing Cholangitis: Preclinical Data in MDR2 Knockout Mice. International journal of molecular sciences, 21 (22). ISSN 1422-0067. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Abstract

Primary Sclerosing Cholangitis (PSC) is a progressive liver disease for which there is no effective medical therapy. PSC belongs to the family of immune-mediated biliary disorders and it is characterized by persistent biliary inflammation and fibrosis. Here, we explored the possibility of using extracellular vesicles (EVs) derived from human, bone marrow mesenchymal stromal cells (MSCs) to target liver inflammation and reduce fibrosis in a mouse model of PSC. Five-week-old male FVB.129P2-Abcb mice were intraperitoneally injected with either 100 µL of EVs (± 9.1 × 10 particles/mL) or PBS, once a week, for three consecutive weeks. One week after the last injection, mice were sacrificed and liver and blood collected for flow cytometry analysis and transaminase quantification. In FVB.129P2-Abcb4 mice, EV administration resulted in reduced serum levels of alkaline phosphatase (ALP), bile acid (BA), and alanine aminotransferase (ALT), as well as in decreased liver fibrosis. Mechanistically, we observed that EVs reduce liver accumulation of both granulocytes and T cells and dampen VCAM-1 expression. Further analysis revealed that the therapeutic effect of EVs is accompanied by the inhibition of NFkB activation in proximity of the portal triad. Our pre-clinical experiments suggest that EVs isolated from MSCs may represent an effective therapeutic strategy to treat patients suffering from PSC.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QW Microbiology. Immunology
WI Digestive system. Gastroenterology
Divisions: Clinical Support > Immunology
Planned IP Care > Gastroentrology
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Depositing User: Mrs Yolande Brookes
Date Deposited: 27 Nov 2020 16:03
Last Modified: 27 Nov 2020 16:03
URI: http://www.repository.uhblibrary.co.uk/id/eprint/3734

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