PMID- 32699656
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2160-4150 (Print)
IS  - 2160-4150 (Electronic)
IS  - 2160-4150 (Linking)
VI  - 9
IP  - 3
DP  - 2020
TI  - ATSC transplantation contributes to liver regeneration following 
      paracetamol-induced acute liver injury through differentiation into hepatic-like 
      cells.
PG  - 36-56
AB  - INTRODUCTION: Drug-induced liver injury (DILI) is a leading cause of acute liver 
      injury (ALI). Acetaminophen (also termed paracetamol), can often be found in 
      drugs that may be abused (i.e., prescription for pain relief). Animal experiments 
      have shown that mesenchymal stem cell transplantation can ameliorate or even 
      reverse hepatic injury. MATERIAL AND METHODS: ALI was induced in Wistar rats 
      using paracetamol. ATSCs were transplanted via the intravenous, portal vein, or 
      intrahepatic route directly onto the liver parenchyma. Histological evaluation 
      was conducted to assess drug-induced injury following transplantation. 
      Fluorescence in situ hybridization (FISH) was used to verify the location of stem 
      cells on the liver parenchyma. The effect of those cells on liver regeneration 
      was tested by immunohistochemistry for hepatic growth factor (HGF). In addition, 
      reverse transcription-quantitative PCR (qRT-PCR) was used to assess hepatic 
      growth factor (HGF), hepatic nuclear factor 4alpha (HNF4alpha), cytochrome P450 1A2 
      (CYP1A2) and alpha-fetoprotein (AFP) mRNA expression. RESULTS: Immunohistochemical 
      staining for HGF was stronger in the transplanted groups than that in the control 
      group (P<0.001). HNF4alpha and HGF mRNA levels were increased on day 7 following 
      transplantation (P<0.001 and P=0.009, respectively). CYP1A2 mRNA levels were also 
      increased (P=0.013) in the intravenous groups, while AFP levels were higher in 
      the intrahepatic groups (P=0.006). ATSC transplantation attenuates ALI injury and 
      promotes liver regeneration. Furthermore, expression of specific hepatic enzymes 
      points to ATSC hepatic differentiation. CONCLUSION: The study showed the positive 
      effects of transplanted adipose tissue stem cells (ATSCs) on liver regeneration 
      (LG) through hepatotrophic factors. Furthermore, increased expression of hepatic 
      specific proteins was recorded in ATSC transplanted groups that indicate stem 
      cells differentiation into hepatic cells.
CI  - AJSC Copyright (c) 2020.
FAU - Feretis, Themistoklis
AU  - Feretis T
AD  - 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian 
      University of Athens, Hippocratio Hospital Athens 11527, Greece.
AD  - Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, 
      Greece.
FAU - Katselis, Charalampos
AU  - Katselis C
AD  - 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian 
      University of Athens, Hippocratio Hospital Athens 11527, Greece.
AD  - Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, 
      Greece.
FAU - Papanikolaou, Ioannis G
AU  - Papanikolaou IG
AD  - 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian 
      University of Athens, Hippocratio Hospital Athens 11527, Greece.
AD  - Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, 
      Greece.
FAU - Apostolou, Konstantinos
AU  - Apostolou K
AD  - 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian 
      University of Athens, Hippocratio Hospital Athens 11527, Greece.
AD  - Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, 
      Greece.
FAU - Tsikalakis, Spyridon
AU  - Tsikalakis S
AD  - Department of Pathology, Medical School, National Kapodistrian University of 
      Athens, Hippocratio Hospital Athens 11527, Greece.
FAU - Toutouzas, Konstantinos G
AU  - Toutouzas KG
AD  - 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian 
      University of Athens, Hippocratio Hospital Athens 11527, Greece.
FAU - Theodoropoulos, George
AU  - Theodoropoulos G
AD  - 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian 
      University of Athens, Hippocratio Hospital Athens 11527, Greece.
FAU - Trigka, Eleni Andrianna
AU  - Trigka EA
AD  - Department of Pathology, Medical School, National Kapodistrian University of 
      Athens, Hippocratio Hospital Athens 11527, Greece.
FAU - Saetta, Angelica A
AU  - Saetta AA
AD  - Department of Pathology, Medical School, National Kapodistrian University of 
      Athens, Hippocratio Hospital Athens 11527, Greece.
FAU - Alexakis, Nicholas
AU  - Alexakis N
AD  - 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian 
      University of Athens, Hippocratio Hospital Athens 11527, Greece.
FAU - Konstandoulakis, Manousos
AU  - Konstandoulakis M
AD  - 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian 
      University of Athens, Hippocratio Hospital Athens 11527, Greece.
FAU - Tsarea, Kalliopi
AU  - Tsarea K
AD  - Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, 
      Greece.
FAU - Karamperi, Maria
AU  - Karamperi M
AD  - Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, 
      Greece.
FAU - Kletsas, Dimitrios
AU  - Kletsas D
AD  - Laboratory of Cell Proliferation & Ageing, Institute of Biology NCSR 'Demokritos' 
      Athens 15310, Greece.
FAU - Patsouris, Efstratios
AU  - Patsouris E
AD  - Department of Pathology, Medical School, National Kapodistrian University of 
      Athens, Hippocratio Hospital Athens 11527, Greece.
FAU - Manouras, Andreas
AU  - Manouras A
AD  - 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian 
      University of Athens, Hippocratio Hospital Athens 11527, Greece.
FAU - Zografos, Georgios C
AU  - Zografos GC
AD  - 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian 
      University of Athens, Hippocratio Hospital Athens 11527, Greece.
FAU - Papalois, Apostolos
AU  - Papalois A
AD  - 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian 
      University of Athens, Hippocratio Hospital Athens 11527, Greece.
AD  - Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, 
      Greece.
AD  - European University Cyprus, Medical School Nicosia 2404, Cyprus.
LA  - eng
PT  - Journal Article
DEP - 20200615
PL  - United States
TA  - Am J Stem Cells
JT  - American journal of stem cells
JID - 101578936
PMC - PMC7364386
OTO - NOTNLM
OT  - Adipose tissue stem cells
OT  - acute liver injury
OT  - cytochrome P450 1A2
OT  - drug-induced liver injury
OT  - hepatic growth factor
OT  - hepatic nuclear factor 4
OT  - liver regeneration
OT  - alpha-fetoprotein
COIS- None.
EDAT- 2020/07/24 06:00
MHDA- 2020/07/24 06:01
PMCR- 2020/06/15
CRDT- 2020/07/24 06:00
PHST- 2020/04/08 00:00 [received]
PHST- 2020/05/12 00:00 [accepted]
PHST- 2020/07/24 06:00 [entrez]
PHST- 2020/07/24 06:00 [pubmed]
PHST- 2020/07/24 06:01 [medline]
PHST- 2020/06/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Stem Cells. 2020 Jun 15;9(3):36-56. eCollection 2020.