PMID- 32513263
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20210618
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Jun 8
TI  - Plasma membrane vesicles of human umbilical cord mesenchymal stem cells 
      ameliorate acetaminophen-induced damage in HepG2 cells: a novel stem cell 
      therapy.
PG  - 225
LID - 10.1186/s13287-020-01738-z [doi]
LID - 225
AB  - BACKGROUND: Acetaminophen (APAP) overdose is the common cause of acute liver 
      failure (ALF) due to the oxidative damage of multiple cellular components. This 
      study aimed to investigate whether plasma membrane vesicles (PMVs) from human 
      umbilical cord mesenchymal stem cells (hUCMSCs) could be exploited as a novel 
      stem cell therapy for APAP-induced liver injury. METHODS: PMVs from hUCMSCs were 
      prepared with an improved procedure including a chemical enucleation step 
      followed by a mechanical extrusion. PMVs of hUCMSCs were characterized and 
      supplemented to hepatocyte cultures. Rescue of APAP-induced hepatocyte damage was 
      evaluated. RESULTS: The hUCMSCs displayed typical fibroblastic morphology and 
      multipotency when cultivated under adipogenic, osteogenic, or chondrogenic 
      conditions. PMVs of hUCMSCs maintained the stem cell phenotype, including the 
      presence of CD13, CD29, CD44, CD73, and HLA-ABC, but the absence of CD45, CD117, 
      CD31, CD34, and HLA-DR on the plasma membrane surface. RT-PCR and transcriptomic 
      analyses showed that PMVs were similar to hUCMSCs in terms of mRNA profile, 
      including the expression of stemness genes GATA4/5/6, Nanog, and Oct1/2/4. GO 
      term analysis showed that the most prominent reduced transcripts in PMVs belong 
      to integral membrane components, extracellular vesicular exosome, and 
      extracellular matrix. Immunofluorescence labeling/staining and confocal 
      microscopy assays showed that PMVs enclosed cellular organelles, including 
      mitochondria, lysosomes, proteasomes, and endoplasmic reticula. Incorporation of 
      the fusogenic VSV-G viral membrane glycoprotein stimulated the endosomal release 
      of PMV contents into the cytoplasm. Further, the addition of PMVs and a 
      mitochondrial-targeted antioxidant Mito-Tempo into cultures of APAP-treated HepG2 
      cells resulted in reduced cell death, enhanced viability, and increased 
      mitochondrial membrane potential. Lastly, this study demonstrated that the redox 
      state and activities of aminotransferases were restored in APAP-treated HepG2 
      cells. CONCLUSIONS: The results suggest that PMVs from hUCMSCs could be used as a 
      novel stem cell therapy for the treatment of APAP-induced liver injury.
FAU - Lin, Mei-Jia
AU  - Lin MJ
AD  - Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine 
      Sciences, Shantou University, Shantou, 515063, Guangdong, China.
FAU - Li, Shuang
AU  - Li S
AD  - Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine 
      Sciences, Shantou University, Shantou, 515063, Guangdong, China.
FAU - Yang, Lu-Jun
AU  - Yang LJ
AD  - Research Center for Translational Medicine, The Second Affiliated Hospital of 
      Shantou University Medical College, Shantou, 515041, Guangdong, China. 
      yanglujun726@hotmail.com.
FAU - Ye, Dan-Yan
AU  - Ye DY
AD  - Research Center for Translational Medicine, The Second Affiliated Hospital of 
      Shantou University Medical College, Shantou, 515041, Guangdong, China.
FAU - Xu, Li-Qun
AU  - Xu LQ
AD  - Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine 
      Sciences, Shantou University, Shantou, 515063, Guangdong, China.
FAU - Zhang, Xin
AU  - Zhang X
AD  - Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou 
      University Medical College, Shantou, 515041, Guangdong, China.
FAU - Sun, Ping-Nan
AU  - Sun PN
AD  - Stem Cell Research Center, Shantou University Medical College, Shantou, 515041, 
      Guangdong, China.
FAU - Wei, Chi-Ju
AU  - Wei CJ
AD  - Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine 
      Sciences, Shantou University, Shantou, 515063, Guangdong, China. 
      chijuwei@stu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200608
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 362O9ITL9D (Acetaminophen)
SB  - IM
MH  - *Acetaminophen/toxicity
MH  - Cell Differentiation
MH  - Cell Membrane
MH  - Cell- and Tissue-Based Therapy
MH  - Hep G2 Cells
MH  - Humans
MH  - *Mesenchymal Stem Cells
MH  - Umbilical Cord
PMC - PMC7278066
OTO - NOTNLM
OT  - Acetaminophen (APAP)
OT  - Acute liver failure (ALF)
OT  - Human umbilical cord mesenchymal stem cells (hUCMSCs)
OT  - Plasma membrane vesicles (PMVs)
OT  - Stem cell therapy
COIS- The authors declare that they have no competing interests.
EDAT- 2020/06/10 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/06/08
CRDT- 2020/06/10 06:00
PHST- 2020/02/25 00:00 [received]
PHST- 2020/05/19 00:00 [accepted]
PHST- 2020/05/12 00:00 [revised]
PHST- 2020/06/10 06:00 [entrez]
PHST- 2020/06/10 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/06/08 00:00 [pmc-release]
AID - 10.1186/s13287-020-01738-z [pii]
AID - 1738 [pii]
AID - 10.1186/s13287-020-01738-z [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2020 Jun 8;11(1):225. doi: 10.1186/s13287-020-01738-z.