Liver fibrosis: Extracellular vesicles mediated intercellular communication in perisinusoidal space

Ezhilarasan, Devaraj; Elumalai, Perumal; Subramaniyan, Raghunandhakumar; Najimi, Mustapha

doi:10.1002/hep.32239

Cited by 43 publications

(28 citation statements)

References 105 publications

(147 reference statements)

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“…Because it is difficult to fully develop severe steatohepatitis and advanced fibrosis by diet-based models ( Guo et al., 2017 ; Liu et al., 2021 ), we therefore focused on the stages of NASH with mild fibrosis after feeding the rats with HFHCD for 16 weeks. This is consistent with the previous opinions that diet-based models are hard to develop advanced fibrosis ( Asgharpour et al., 2016 ; Tsuchida et al., 2018 ) In the NASH progression, quiescent HSCs are transformed into activated HSCs ( Devaraj et al., 2021 ; Zisser et al., 2021 ). Hepatic macrophages are involved in the activation of HSCs.…”

Section: Discussionsupporting

confidence: 93%

M2 macrophage-derived exosomal microRNA-411-5p impedes the activation of hepatic stellate cells by targeting CAMSAP1 in NASH model

et al. 2022

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Section: Discussionsupporting

confidence: 93%

M2 macrophage-derived exosomal microRNA-411-5p impedes the activation of hepatic stellate cells by targeting CAMSAP1 in NASH model

et al. 2022

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“…Considerable evidence has suggested that exosomes have important roles not only in the pathogenic progression of chronic liver disease but also in the initial onset of acute liver injury. [113][114][115] HSC-derived exosomes are considered to be one of the most prominent indicators of the degree of liver damage, 21 which is supported by a series of experimental studies. To date, most investigations of HSC-derived exosomes on liver damage have focused on chronic liver injury and persisting consequences that result in acute liver injury.…”

Section: Acute Liver Injurymentioning

confidence: 90%

Unraveling the Emerging Niche Role of Hepatic Stellate Cell-derived Exosomes in Liver Diseases

Yin¹,

Li²,

Song³

et al. 2022

J Clin Transl Hepatol

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Hepatic stellate cells (HSCs) play an essential role in various liver diseases, and exosomes are critical mediators of intercellular communication in local and distant microenvironments. Cellular crosstalk between HSCs and surrounding multiple tissue-resident cells promotes or inhibits the activation of HSCs. Substantial evidence has revealed that HSC-derived exosomes are involved in the occurrence and development of liver diseases through the regulation of retinoid metabolism, lipid metabolism, glucose metabolism, protein metabolism, and mitochondrial metabolism. HSCderived exosomes are underpinned by vehicle molecules, such as mRNAs and microRNAs, that function in, and significantly affect, the processes of various liver diseases, such as acute liver injury, alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, fibrosis, and cancer. As such, numerous exosomes derived from HSCs or HSCassociated exosomes have attracted attention because of their biological roles and translational applications as potential targets for therapeutic targets. Herein, we review the pathophysiological and metabolic processes associated with HSC-derived exosomes, their roles in various liver diseases and their potential clinical application.

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“…2 Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China. 3 Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, China. 4 Guangzhou Key Laboratory for Surface Chemistry of Energy Materials, New Energy Research Institute, School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou, China.…”

Section: Author Contributionsmentioning

confidence: 99%

“…Chronic liver disease is responsible for approximately 2 million global deaths per year, as well as a large economic burden and increased healthcare utilization [ 1 ]. Hepatic fibrosis initiated as a result of chronic liver injury due to virus infection, alcoholic liver disease, nonalcoholic fatty liver disease, drug toxicity, metabolic disorders and autoimmune disease, is believed to initiate the deterioration of liver architecture [ 2 , 3 ]. Liver fibrosis is characterized by excessive accumulation of extracellular matrix (ECM), and aHSCs are the main cell population for the ECM [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Huc-MSC-derived exosomes modified with the targeting peptide of aHSCs for liver fibrosis therapy

Yan

Bai

et al. 2022

J Nanobiotechnol

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Background Effective therapeutics to stop or reverse liver fibrosis have not emerged, because these potential agents cannot specifically target activated hepatic stellate cells (aHSCs) or are frequently toxic to parenchymal cells. Human umbilical cord mesenchymal stem cell (Huc-MSC)-derived exosomes show promise in nanomedicine for the treatment of liver fibrosis. However, systemic injection showed that unmodified exosomes were mainly taken up by the mononuclear phagocyte system. The discovery of ligands that selectively bind to a specific target plays a crucial role in clinically relevant diagnostics and therapeutics. Herein, we aimed to identify the targeting peptide of aHSCs by screening a phage-displayed peptide library, and modify Huc-MSC-derived exosomes with the targeting peptide. Results In this study, we screened a phage-displayed peptide library by biopanning for peptides preferentially bound to HSC-T6 cells. The identified peptide, HSTP1, also exhibited better targeting ability to aHSCs in pathological sections of fibrotic liver tissues. Then, HSTP1 was fused with exosomal enriched membrane protein (Lamp2b) and was displayed on the surface of exosomes through genetic engineering technology. The engineered exosomes (HSTP1-Exos) could be more efficiently internalized by HSC-T6 cells and outperformed both unmodified exosomes (Blank-Exos) and Lamp2b protein overexpressed exosomes (Lamp2b + Exos) in enhancing the ability of exosomes to promote HSC-T6 reversion to a quiescent phenotype. In vivo results showed HSTP1-Exos could specifically target to the aHSC region after intravenous administration, as demonstrated by coimmunofluorescence with the typical aHSCs marker α-SMA, and enhance the therapeutic effect on liver fibrosis. Conclusion These results suggest that HSTP1 is a reliable targeting peptide that can specifically bind to aHSCs and that HSTP1-modified exosomes realize the precise treatment for aHSCs in complex liver tissue. We provide a novel strategy for clinical liver fibrosis therapy. Graphical Abstract

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Liver fibrosis: Extracellular vesicles mediated intercellular communication in perisinusoidal space

Cited by 43 publications

References 105 publications

M2 macrophage-derived exosomal microRNA-411-5p impedes the activation of hepatic stellate cells by targeting CAMSAP1 in NASH model

M2 macrophage-derived exosomal microRNA-411-5p impedes the activation of hepatic stellate cells by targeting CAMSAP1 in NASH model

Unraveling the Emerging Niche Role of Hepatic Stellate Cell-derived Exosomes in Liver Diseases

Huc-MSC-derived exosomes modified with the targeting peptide of aHSCs for liver fibrosis therapy

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