PMID- 36371344
OWN - NLM
STAT- MEDLINE
DCOM- 20221115
LR  - 20221117
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 13
IP  - 1
DP  - 2022 Nov 12
TI  - Human umbilical cord mesenchymal stromal cell-derived exosomes protect against 
      MCD-induced NASH in a mouse model.
PG  - 517
LID - 10.1186/s13287-022-03201-7 [doi]
LID - 517
AB  - BACKGROUND AND AIMS: Human umbilical cord mesenchymal stem cells (hUC-MSCs) are 
      increasingly being studied in clinical trials of end-stage liver disease because 
      of their good tissue repair and anti-inflammatory effects. hUC-MSC exosomes are 
      vesicles with spherical structures secreted by cells that produce them. The 
      diameter of exosomes is much smaller than that of hUC-MSCs, suggesting that 
      exosomes might be a novel and safer therapeutic product of mesenchymal stem 
      cells. As exosomes have been suggested to have biochemical functions similar to 
      those of hUC-MSCs, this study investigated the efficiency of hUC-MSC-derived 
      exosomes in protecting against nonalcoholic steatohepatitis using an MCD-induced 
      mouse model. METHODS: Human umbilical cord mesenchymal stem cell-derived exosomes 
      were extracted and purified. The effect of these exosomes on disease progression 
      in an MCD-induced nonalcoholic steatohepatitis mouse model was investigated. 
      RESULTS: The results showed that UC-MSC exosomes intravenously transplanted into 
      mice with MCD-induced NASH improved MCD-induced body weight loss and liver damage 
      in a mouse model. Additionally, the inflammatory cytokines in liver tissue were 
      reduced, which may be caused by exosome-induced macrophage anti-inflammatory 
      phenotypes both in vitro and in vivo. In addition, UC-MSC exosomes reversed PPARalpha 
      level in ox-LDL-treated hepatocytes in vitro and in NASH mouse liver, which had 
      been downregulated. CONCLUSIONS: UC-MSC exosomes alleviate MCD-induced NASH in 
      mice by regulating the anti-inflammatory phenotype of macrophages and by 
      reversing PPARalpha protein expression in liver cells, which holds great potential in 
      NASH therapy.
CI  - (c) 2022. The Author(s).
FAU - Shi, Ying
AU  - Shi Y
AD  - Hepatology Department, First Hospital of Jilin University, No. 1, Xinmin Street, 
      Changchun, 130000, Jilin, People's Republic of China.
FAU - Yang, Xiaoguang
AU  - Yang X
AD  - National Engineering Laboratory for Druggable Gene and Protein Screening, 
      Northeast Normal University, 2555 JingYue Street, Changchun, 130000, Jilin, 
      People's Republic of China.
FAU - Wang, Shuyue
AU  - Wang S
AD  - National Engineering Laboratory for Druggable Gene and Protein Screening, 
      Northeast Normal University, 2555 JingYue Street, Changchun, 130000, Jilin, 
      People's Republic of China.
FAU - Wu, Yulun
AU  - Wu Y
AD  - National Engineering Laboratory for Druggable Gene and Protein Screening, 
      Northeast Normal University, 2555 JingYue Street, Changchun, 130000, Jilin, 
      People's Republic of China.
FAU - Zheng, Lihua
AU  - Zheng L
AD  - National Engineering Laboratory for Druggable Gene and Protein Screening, 
      Northeast Normal University, 2555 JingYue Street, Changchun, 130000, Jilin, 
      People's Republic of China.
FAU - Tang, Yufang
AU  - Tang Y
AD  - Biomedical Laboratory Center of Wish Vocational Training School, Beihu Science 
      and Technology Zone, Changchun, 130012, Jilin, People's Republic of China.
FAU - Gao, Yanhang
AU  - Gao Y
AD  - Hepatology Department, First Hospital of Jilin University, No. 1, Xinmin Street, 
      Changchun, 130000, Jilin, People's Republic of China. yanhang@mail.jlu.edu.cn.
FAU - Niu, Junqi
AU  - Niu J
AD  - Hepatology Department, First Hospital of Jilin University, No. 1, Xinmin Street, 
      Changchun, 130000, Jilin, People's Republic of China. junqiniu@jlu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221112
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (PPAR alpha)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Exosomes/metabolism
MH  - *Non-alcoholic Fatty Liver Disease/therapy/metabolism
MH  - PPAR alpha/metabolism
MH  - Umbilical Cord
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Disease Models, Animal
MH  - *Mesenchymal Stem Cell Transplantation
PMC - PMC9652856
OTO - NOTNLM
OT  - MCD mouse model
OT  - Nonalcoholic steatohepatitis
OT  - PPARalpha
OT  - hUC-MSC exosomes
COIS- There are no competing interests.
EDAT- 2022/11/13 06:00
MHDA- 2022/11/16 06:00
PMCR- 2022/11/12
CRDT- 2022/11/12 23:45
PHST- 2021/09/02 00:00 [received]
PHST- 2022/03/28 00:00 [accepted]
PHST- 2022/11/12 23:45 [entrez]
PHST- 2022/11/13 06:00 [pubmed]
PHST- 2022/11/16 06:00 [medline]
PHST- 2022/11/12 00:00 [pmc-release]
AID - 10.1186/s13287-022-03201-7 [pii]
AID - 3201 [pii]
AID - 10.1186/s13287-022-03201-7 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2022 Nov 12;13(1):517. doi: 10.1186/s13287-022-03201-7.