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

1
Department of Biomedical Sciences, University of Padova and Fondazione Istituto di Ricerca Pediatrica—Città della Speranza, 35127 Padova, Italy
2
National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham; Centre for Liver and GI Research, Institute of Immunology and Immunotherapy, University of Birmingham; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK
3
Department of Surgery, Oncology and Gastroenterology—DiSCOG, Gastroenterology and Multivisceral Transplant Unit, 35128 Padova, Italy
4
Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands
5
Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padova, and Stem Cell and Regenerative Medicine Laboratory, Department of Women’s and Children’s Health, University of Padova, 35128 Padova, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Int. J. Mol. Sci. 2020, 21(22), 8874; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228874
Received: 12 October 2020 / Revised: 5 November 2020 / Accepted: 11 November 2020 / Published: 23 November 2020
(This article belongs to the Section Biochemistry)
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-Abcb4tm1Bor mice were intraperitoneally injected with either 100 µL of EVs (± 9.1 × 109 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-Abcb4tm1Bor 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. View Full-Text
Keywords: inflammation; fibrosis; mesenchymal stromal cells; liver; therapy inflammation; fibrosis; mesenchymal stromal cells; liver; therapy
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MDPI and ACS Style

Angioni, R.; Calì, B.; Vigneswara, V.; Crescenzi, M.; Merino, A.; Sánchez-Rodríguez, R.; Liboni, C.; Hoogduijn, M.J.; Newsome, P.N.; Muraca, M.; Russo, F.P.; Viola, A. Administration of Human MSC-Derived Extracellular Vesicles for the Treatment of Primary Sclerosing Cholangitis: Preclinical Data in MDR2 Knockout Mice. Int. J. Mol. Sci. 2020, 21, 8874. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228874

AMA Style

Angioni R, Calì B, Vigneswara V, Crescenzi M, Merino A, Sánchez-Rodríguez R, Liboni C, Hoogduijn MJ, Newsome PN, Muraca M, Russo FP, Viola A. 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. 2020; 21(22):8874. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228874

Chicago/Turabian Style

Angioni, Roberta, Bianca Calì, Vasanthy Vigneswara, Marika Crescenzi, Ana Merino, Ricardo Sánchez-Rodríguez, Cristina Liboni, Martin J. Hoogduijn, Philip N. Newsome, Maurizio Muraca, Francesco P. Russo, and Antonella Viola. 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, no. 22: 8874. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228874

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