Mesenchymal Stem Cells-Derived Exosomes as Dexamethasone Delivery Vehicles for Autoimmune Hepatitis Therapy.

Jiawei Zhao,Yue Li,Min Shi,Rongrong Jia,Yugang Wang,Jinghui Wang

doi:10.3389/fbioe.2021.650376

Abstract

Exosomes (Exos) are nanosized vesicles (around 100 nm) that recently serve as a promising drug carrier with high biocompatibility and low immunogenicity. Previous studies showed that Exos secreted from mesenchymal stem cells (MSCs) provide protection for concanavalin A (Con A)-induced liver injury. In this study, the protective effect of Exos is confirmed, and dexamethasone (DEX)-incorporated Exos named Exo@DEX are prepared. It is then investigated whether Exo@DEX can function more efficiently compared to free drugs and naive Exos in a Con A-induced autoimmune hepatitis (AIH) mouse model. The results show that Exo@DEX efficiently improves the accumulation of DEX in AIH in the liver. These data suggest that Exo@DEX is a promising drug carrier for AIH and could have applications in other diseases.

Highlights

Autoimmune hepatitis (AIH) is characterized by a mild increase in serum transaminase concurrent with increased immunoglobulin G and circulating autoantibodies (Strassburg, 2010)
We developed a liver-targeting Exo@DEX delivery system by loading dexamethasone (DEX) into MSCderived Exos for the treatment of concanavalin A (Con A)-induced autoimmune hepatitis (AIH) (Bartneck et al, 2015)
Exosomes were purified from cell culture supernatants of mesenchymal stem cells (MSCs) and were further loaded with DEX by water bath sonication

Summary

Introduction

Autoimmune hepatitis (AIH) is characterized by a mild increase in serum transaminase concurrent with increased immunoglobulin G and circulating autoantibodies (Strassburg, 2010). The first-line therapy for AIH is prednisone combined with azathioprine. High doses of steroids could spread into the whole body and contribute to AIH patients abandoning such treatment due to drug complications (such as Cushing’s syndrome, hypertension, peptic ulcer, infection, and neurological symptoms) (Violatto et al, 2019). AIH could be exacerbated into liver fibrosis or even cirrhosis of the liver if the disease is badly controlled and that is when liver transplantation becomes a necessity. Some artificially synthetic nanoparticles are still facing some problems, such as poor biocompatibility and biotoxicity

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Conclusion