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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; Viola, Antonella.
Affiliation
  • Angioni R; Department of Biomedical Sciences, University of Padova and Fondazione Istituto di Ricerca Pediatrica-Città della Speranza, 35127 Padova, Italy.
  • Calì B; Department of Biomedical Sciences, University of Padova and Fondazione Istituto di Ricerca Pediatrica-Città della Speranza, 35127 Padova, Italy.
  • Vigneswara V; 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 Birmingh
  • Crescenzi M; Department of Surgery, Oncology and Gastroenterology-DiSCOG, Gastroenterology and Multivisceral Transplant Unit, 35128 Padova, Italy.
  • Merino A; Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands.
  • Sánchez-Rodríguez R; Department of Biomedical Sciences, University of Padova and Fondazione Istituto di Ricerca Pediatrica-Città della Speranza, 35127 Padova, Italy.
  • Liboni C; Department of Biomedical Sciences, University of Padova and Fondazione Istituto di Ricerca Pediatrica-Città della Speranza, 35127 Padova, Italy.
  • Hoogduijn MJ; Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands.
  • Newsome PN; 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 Birmingh
  • Muraca M; 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.
  • Russo FP; Department of Surgery, Oncology and Gastroenterology-DiSCOG, Gastroenterology and Multivisceral Transplant Unit, 35128 Padova, Italy.
  • Viola A; Department of Biomedical Sciences, University of Padova and Fondazione Istituto di Ricerca Pediatrica-Città della Speranza, 35127 Padova, Italy.
Int J Mol Sci ; 21(22)2020 Nov 23.
Article in En | MEDLINE | ID: mdl-33238629
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-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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cholangitis, Sclerosing / ATP Binding Cassette Transporter, Subfamily B / Inflammation / Liver Limits: Animals / Humans Language: En Journal: Int J Mol Sci Year: 2020 Document type: Article Affiliation country: Italy

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cholangitis, Sclerosing / ATP Binding Cassette Transporter, Subfamily B / Inflammation / Liver Limits: Animals / Humans Language: En Journal: Int J Mol Sci Year: 2020 Document type: Article Affiliation country: Italy