Application of exosome in liver diseases

Introduction

Over the past few decades, extracellular vesicles (EVs) including exosomes have attracted great attention in the scientific community due to their essential functions in intercellular communication and their potential roles in the development and progression of various diseases. One specific type of EVs, known as exosomes, have been recognized as crucial mediators in a broad range of biological processes, such as cell proliferation, differentiation, and immune regulation. More importantly, the potential therapeutic applications of exosomes in various diseases have been explored extensively. In this review, we concentrate on the utilization of exosomes in the treatment of liver-related diseases and summarize the current progress in exosome-based therapy.

Exosomes in liver-related diseases

The liver is a vital organ that performs many essential physiological functions. However, liver-related diseases, including hepatitis, liver fibrosis, and liver cancer, have become major health issues worldwide. Despite significant progress in developing pharmacological therapies, these diseases still have high morbidity and mortality rates. In recent years, exosome-based therapy has emerged as a promising approach to the treatment of liver-related diseases.

Exosomes derived from different sources have been shown to have therapeutic effects in various liver-related diseases. For example, exosomes from mesenchymal stem cells (MSCs) have been reported to attenuate liver fibrosis by suppressing hepatic stellate cell activation and promoting hepatocyte proliferation [1]. In addition, exosomes from dendritic cells have been shown to alleviate liver injury by modulating T-cell immune responses [2]. Furthermore, hepatocyte-derived exosomes have been demonstrated to promote liver regeneration and ameliorate liver fibrosis [3]. These studies suggest that exosomes can regulate various aspects of liver biology and have potential therapeutic applications in treating liver-related diseases.

Exosome-based therapy in liver-related diseases

Exosomes are promising drug delivery vehicles due to their ability to carry a diverse range of molecules, including proteins, nucleic acids, and lipids. Moreover, exosomes are more biocompatible and less immunogenic than other types of vesicles, making them an ideal vehicle for drug delivery [4]. In the context of liver-related diseases, exosomes have been explored as therapeutic agents for the following applications:

1. Delivery of therapeutic RNA molecules: RNA-based therapies have shown remarkable potential in the treatment of liver-related diseases. Exosomes can deliver various RNA molecules, such as siRNA, miRNA, and lncRNA, to target cells and exert therapeutic effects [5]. For instance, exosome-mediated delivery of miR-122 has been demonstrated to suppress hepatitis C virus replication and reduce liver fibrosis [6]. Moreover, exosome-mediated delivery of siRNA targeting pro-fibrotic genes has been shown to attenuate liver fibrosis [7]. These studies suggest that exosomes can be used as efficient carriers for RNA-based therapies in liver-related diseases.

2. Delivery of therapeutic enzymes: Liver-related diseases are often accompanied by the accumulation of toxic metabolites, which can cause liver damage and impair liver function. Therapeutic enzymes, such as catalase and superoxide dismutase, have been explored for the treatment of liver-related diseases. However, their therapeutic efficacy is limited by their poor stability and low bioavailability. Exosomes can carry therapeutic enzymes and protect them from degradation. For example, exosomes loaded with catalase have been shown to attenuate liver injury and oxidative stress in mouse models of liver fibrosis [8]. These results suggest that exosomes can be employed as delivery vehicles for therapeutic enzymes in liver-related diseases.

3. Immunomodulation: The liver has a unique immune microenvironment, which plays a crucial role in both liver injury and repair. Exosomes derived from immune cells, such as dendritic cells and macrophages, have been shown to modulate immune responses in various liver-related diseases. For example, exosomes derived from dendritic cells have been shown to promote T-cell differentiation and ameliorate liver injury in a mouse model of autoimmune hepatitis [9]. Furthermore, exosomes derived from macrophages have been shown to alleviate liver inflammation and fibrosis in mouse models of Non-alcoholic steatohepatitis (NASH) [10]. These studies suggest that exosomes can modulate immune responses and potentially treat liver-related diseases.

Future perspectives

Despite the promising results, there are still several challenges that need to be addressed before exosome-based therapy can be widely applied in clinical settings. Firstly, the methods for exosome isolation and purification need to be optimized to obtain high-quality, pure exosomes for therapeutic purposes. Secondly, long-term safety and efficacy studies are needed to evaluate the potential risks and benefits of exosome-based therapy. Thirdly, standardized protocols for exosome characterization and functional assessment are needed to facilitate the comparison of results across different studies.

Conclusion

In conclusion, exosome-based therapy is a promising approach for the treatment of liver-related diseases. Exosomes can regulate various aspects of liver biology and have the potential to deliver therapeutic agents efficiently. However, further studies are needed to optimize their isolation, purification, and characterization for clinical applications. As the field advances, exosome-based therapy may offer a valuable treatment option for liver-related diseases.

References:

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8. Wang J, et al. (2020) Exosomes from bone marrow-derived mesenchymal stem cells overexpressing catalase attenuate liver fibrosis. Int J Nanomedicine 15, 2029–2045.

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