Stem cell exosomes: new hope and future potential for relieving liver fibrosis

Abstract

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Keywords: Autophagy; Exosomes; Hepatic fibrosis; Inflammation factor; Oxidative stress.

Figure 1.

The nucleic acids and proteins produced by the nucleus and organelles, as well as substances taken up through endocytosis, together form early endosomes, which are then expelled from the cell through exocytosis. There are various functional substances present in the exocrine body and it s surface, such as proteins, DNA, miRNA, etc.

Figure 2.

LPS and IFN-γ induce M1 macrophages, whereas IL-4 and IL-13 induce M2 macrophages. Exosomes containing specific miRNAs derived from stem cells can modulate the polarization of macrophages. This modulation enables pro-inflammatory M1 macrophages to transform into anti-inflammatory M2 macrophages.

Figure 3.

The interaction between exosomes and autophagy significantly impacts the progression of liver fibrosis. (I) To summarize, autophagy occurs in both parenchymal and non-parenchymal cells of the liver. This process can help mitigate liver fibrosis. (II) When autophagy in hepatocytes is inhibited, the release of exosomes increases. (III) When platelet-derived growth factor activates hepatic stellate cells, blocking their autophagy leads to an increase in exosome release. (IV) AMSC-Exosomes and BMSC-Exosomes help prevent liver fibrosis by promoting the process of autophagy.

Figure 4.

Exosomes of different cellular origins can alleviate liver fibrosis via regulating TGF-β/Smad pathway.