• Research on the effects of exosomes derived from liver cells in treatment of liver diseases
  • Niloofar Torkzadeh,1,* Mozhgan shirazi,2
    1. Department of Biochemistry, Islamic Azad University, Falavarjan,Iran
    2. Department of Biology, Scince and Reserch Branch, Islamic Azad University, Tehran, iran


  • Introduction: Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have been widely reported as promising cell free products that show therapeutic effects of the parental cells but not their limitations. The most effective treatment for end stage liver fibrosis is currently liver transplantations, however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases.
  • Methods: We reviewed about 22 articles were conducted from 2017 to 2021 in the world and Iran. We searched some key words such as mesenchymal stromal cells, exosome, liver cirrhosis, immune modulation, trophic factors, liver fibrosis in Science direct, Elsevier, PubMed and SID.
  • Results: MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immunomodulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte, regeneration, regress liver fibrosis and enhance liver functionality. Exosomes are extracellular vesicles with diameters ranging from 30 to 150nm, which contain several donor cell associated proteins as well as mRNA, miRNA, and lipids and coordinate multiple physiological and pathological functions through horizontal communication between cell. Almost all types of liver cells, such as hepatocytes and kupffer cells, are exosome releasing and /or exosome targeted cells. Exosomes secreted by liver cells play an important role in regulating general physiological functions and also participate in the onset and development of (liver) diseases, including liver cancer, liver injury, liver fibrosis and viral hepatitis. Liver cell derived exosomes carry liver cell specific proteins and miRNAs, which can be used as diagnostic biomarkers and treatment targets of liver disease. Researchers have demonstrated that miRNA_122 loaded in exosomes derived from mesenchymal stem cells (MSCs) can inhibit the activation and proliferation of primary HSCs, and continued treatment for 4 weeks using this method can improve ccl4 induced liver fibrosis in mice. Ohara et al. demonstrated that amniotic mesenchymal stem cell derived extracellular vesicles in primary cell culture can suppress the activation of kupffer cells and HSCs and can improve ccl4 induced liver fibrosis. Exosome derived from human umbilical cord mesenchymal stem cells (HUC_MSCs) also reduce fibrosis by inhibiting the expression of collagen and TGF_β1 in vivo. In addition, MSC derived exosomes suppress liver fibrosis by improving liver function and inhibiting inflammation and HSC activation. In HCV induced fibrosis, HCV replicating hepatocytes transfer miRNA192 to HSCs through exosomes, activating HSCs and inducing their trans differentiation into myofibroblasts. This suggests that exosomal miR_192 is major regulator and potential therapeutic target in liver fibrosis induced by HCV.
  • Conclusion: This review discusses the functions of exosome derived from different liver cells and provides novel insights based on the latest developments regarding the roles of exosome in the diagnosis and treatment of liver diseases. We also present several outstanding risks, including
  • Keywords: Exosome, liver cirrhosis, immune modulation, trophic factors, Extracellular vesicles