Extracellular Vesicles from Amnion-Derived Mesenchymal Stem Cells Ameliorate Hepatic Inflammation and Fibrosis in Rats
Joint Authors
Ohnishi, Shunsuke
Sakamoto, Naoya
Ohara, Masatsugu
Hosono, Hidetaka
Yamamoto, Koji
Yuyama, Kohei
Nakamura, Hideki
Fu, Qingjie
Maehara, Osamu
Suda, Goki
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-12-24
Country of Publication
Egypt
No. of Pages
15
Abstract EN
Background.
There are no approved drug treatments for liver fibrosis and nonalcoholic steatohepatitis (NASH), an advanced stage of fibrosis which has rapidly become a major cause of cirrhosis.
Therefore, development of anti-inflammatory and antifibrotic therapies is desired.
Mesenchymal stem cell- (MSC-) based therapy, which has been extensively investigated in regenerative medicine for various organs, can reportedly achieve therapeutic effect in NASH via paracrine action.
Extracellular vesicles (EVs) encompass a variety of vesicles released by cells that fulfill functions similar to those of MSCs.
We herein investigated the therapeutic effects of EVs from amnion-derived MSCs (AMSCs) in rats with NASH and liver fibrosis.
Methods.
NASH was induced by a 4-week high-fat diet (HFD), and liver fibrosis was induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) twice a week for six weeks.
AMSC-EVs were intravenously injected at weeks 3 and 4 in rats with NASH (15 μg/kg) and at week 3 in rats with liver fibrosis (20 μg/kg).
The extent of inflammation and fibrosis was evaluated with quantitative reverse transcription polymerase chain reaction and immunohistochemistry.
The effect of AMSC-EVs on inflammatory and fibrogenic response was investigated in vitro.
Results.
AMSC-EVs significantly decreased the number of Kupffer cells (KCs) in the liver of rats with NASH and the mRNA expression levels of inflammatory cytokines such as tumor necrosis factor- (Tnf-) α, interleukin- (Il-) 1β and Il-6, and transforming growth factor- (Tgf-) β.
Furthermore, AMSC-EVs significantly decreased fiber accumulation, KC number, and hepatic stellate cell (HSC) activation in rats with liver fibrosis.
In vitro, AMSC-EVs significantly inhibited KC and HSC activation and suppressed the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signaling pathway.
Conclusions.
AMSC-EVs ameliorated inflammation and fibrogenesis in a rat model of NASH and liver fibrosis, potentially by attenuating HSC and KC activation.
AMSC-EV administration should be considered as a new therapeutic strategy for chronic liver disease.
American Psychological Association (APA)
Ohara, Masatsugu& Ohnishi, Shunsuke& Hosono, Hidetaka& Yamamoto, Koji& Yuyama, Kohei& Nakamura, Hideki…[et al.]. 2018. Extracellular Vesicles from Amnion-Derived Mesenchymal Stem Cells Ameliorate Hepatic Inflammation and Fibrosis in Rats. Stem Cells International،Vol. 2018, no. 2018, pp.1-15.
https://search.emarefa.net/detail/BIM-1213320
Modern Language Association (MLA)
Ohara, Masatsugu…[et al.]. Extracellular Vesicles from Amnion-Derived Mesenchymal Stem Cells Ameliorate Hepatic Inflammation and Fibrosis in Rats. Stem Cells International No. 2018 (2018), pp.1-15.
https://search.emarefa.net/detail/BIM-1213320
American Medical Association (AMA)
Ohara, Masatsugu& Ohnishi, Shunsuke& Hosono, Hidetaka& Yamamoto, Koji& Yuyama, Kohei& Nakamura, Hideki…[et al.]. Extracellular Vesicles from Amnion-Derived Mesenchymal Stem Cells Ameliorate Hepatic Inflammation and Fibrosis in Rats. Stem Cells International. 2018. Vol. 2018, no. 2018, pp.1-15.
https://search.emarefa.net/detail/BIM-1213320
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1213320