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

2020 ◽  
Vol 21 (22) ◽  
pp. 8874
Author(s):  
Roberta Angioni ◽  
Bianca Calì ◽  
Vasanthy Vigneswara ◽  
Marika Crescenzi ◽  
Ana Merino ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Extracellular Vesicles ◽  
Sclerosing Cholangitis ◽  
Serum Levels ◽  
Portal Triad ◽  
Immune Mediated ◽  
Nfkb Activation ◽  
Effective Therapeutic Strategy ◽  
Progressive Liver Disease ◽  
Clinical Experiments

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.

scholarly journals Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma

Hepatology ◽  
2017 ◽  
Vol 66 (4) ◽  
pp. 1125-1143 ◽  
Author(s):  
Ander Arbelaiz ◽  
Mikel Azkargorta ◽  
Marcin Krawczyk ◽  
Alvaro Santos-Laso ◽  
Ainhoa Lapitz ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Extracellular Vesicles ◽  
Sclerosing Cholangitis ◽  
Protein Biomarkers

scholarly journals Association Between HLA Haplotypes and Increased Serum Levels of IgG4 in Patients With Primary Sclerosing Cholangitis

2015 ◽  
Vol 148 (5) ◽  
pp. 924-927.e2 ◽  
Author(s):  
Natalie L. Berntsen ◽  
Olav Klingenberg ◽  
Brian D. Juran ◽  
Maria Benito de Valle ◽  
Björn Lindkvist ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Serum Levels ◽  
Hla Haplotypes

scholarly journals Autoimmune Hepatitis and Primary Sclerosing Cholangitis: An Overlap Syndrome Resistant to Azathioprine and Intolerant to Tacrolimus with Sepsis Mimicking Flare UP-A Clinical Dilemma

2020 ◽  
Vol 07 (02) ◽  
pp. 11-14
Author(s):  
Sharon T Mathews ◽  
Keyword(s):  
Liver Disease ◽  
Autoimmune Hepatitis ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Kidney Injury ◽  
Scoring Systems ◽  
Overlap Syndrome ◽  
Rare Presentation ◽  
First Line Therapy ◽  
Progressive Liver Disease

Patients with autoimmune liver disease in a frequency of 7% -18% fit into the diagnostic criteria for more than one condition. Up to 12.5% of Autoimmune Hepatitis (AIH) and Primary Sclerosing Cholangitis (PSC) cohorts have a label of AIH/PSC overlap. There can be an unpredictable interval of many years between the diagnosis of the two conditions. There are scoring systems but no established criteria for the diagnosis of AIH/PSC overlap. Therefore, a diagnosis based on combination of biochemistry, autoantibody profile, cholangiogram, and liver histologyis made. Histopathology staging of AIH/PSC overlap influences therapeutic options and prognosis. There is beneficial role of immunosuppression, even though there is a higher relapse rate and evidence of progressive liver disease despite immunosuppression in some cases. Liver related outcomes in this overlap are better than PSC alone but are poorer than AIH. We herein report a rare presentation of an overlap syndrome with AIH and PSC in a patient in whom, treatment with first line therapy showed incomplete response and the salvage therapy was not tolerated, presenting with Acute Kidney Injury (AKI) and a clinical picture of sepsis resembling AIH flare.

scholarly journals Primary Sclerosing Cholangitis: Therapeutic Options and Surveillance Management

2016 ◽  
Vol 9 ◽  
pp. CGast.S38451 ◽  
Author(s):  
Aditi Kumar ◽  
Daniel Wheatley ◽  
Amar Puttanna
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Disease Recurrence ◽  
Evidence Base ◽  
Therapeutic Options ◽  
Weak Evidence ◽  
Immune Mediated ◽  
Metabolic Bone ◽  
Bowel Disorders ◽  
Risk Of Disease

Primary sclerosing cholangitis is a chronic immune-mediated liver disease. Though rare, it poses several clinical concerns for the managing physician. There are currently limited therapeutic options in the management of the condition and weak evidence base behind them. Endoscopic intervention is limited to those patients with obstructing stricture-related disease, and even liver transplantation has a risk of disease recurrence. Surveillance for inflammatory bowel disorders, metabolic bone disease, and malignancy is paramount when managing such patients. This article provides an overview of the condition with further focus on current therapeutic options and guidance on surveillance management.

Immune-mediated diseases in primary sclerosing cholangitis

2011 ◽  
Vol 43 (10) ◽  
pp. 802-806 ◽  
Author(s):  
Laetitia E. Lamberts ◽  
Marcel Janse ◽  
Elizabeth B. Haagsma ◽  
Arie P. van den Berg ◽  
Rinse K. Weersma
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Immune Mediated
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