Abstract

BackgroundCirrhosis is a chronic liver disease whereby scar tissue replaces healthy liver parenchyma, leading to disruption of the liver architecture and hepatic dysfunction. Currently, there is no effective disease-modifying therapy for liver fibrosis. Recently, our group demonstrated that human umbilical cord blood (UCB) plasma possesses therapeutic effects in a rat model of acute liver failure.MethodsIn the current study, we tested whether exosomes (Exo) existed in UCB plasma and if they produced any antifibrotic benefits in a liver fibrosis model.ResultsOur results showed that UCB-Exo improved liver function and increased matrix metalloproteinase/tissue inhibitor of metalloproteinase degradation to reduce the degree of fibrosis. Moreover, UCB-Exo were found to suppress hepatic stellate cell (HSC) activity in vitro. These effects were associated with suppression of transforming growth factor-β/inhibitor of DNA binding 1 signaling.ConclusionsThese results further support that UCB-Exo have antifibrotic effects in mice with liver fibrosis and activated HSCs and may herald a new cell-free antifibrotic therapy.

Highlights

  • Liver fibrosis is a healing process associated with chronic inflammation

  • Isolation and identification of exosomes derived from umbilical cord blood (UCB) and peripheral blood (PB) Our previous experiments showed that UCB contains a variety of cytokines with therapeutic effects in the acute liver failure rat model

  • We believed that UCB may contain exosomes that could be used as therapeutic agents

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Summary

Introduction

Liver fibrosis is a healing process associated with chronic inflammation. Fibrogenesis is a vicious cycle driven by a number of damaging factors including inflammation and oxidative stress that underlie various liver conditions, such as hepatitis B and C, alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), and autoimmune liver diseases [1]. Hepatic stellate cells (HSCs) play a central role in liver fibrosis. ID1 levels are highly expressed in hepatocellular carcinoma [9, 10]. Inhibition of ID1 expression may be a promising therapeutic approach. Cirrhosis is a chronic liver disease whereby scar tissue replaces healthy liver parenchyma, leading to disruption of the liver architecture and hepatic dysfunction. There is no effective disease-modifying therapy for liver fibrosis. Our group demonstrated that human umbilical cord blood (UCB) plasma possesses thera‐ peutic effects in a rat model of acute liver failure

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