ATSC transplantation contributes to liver regeneration following paracetamol-induced acute liver injury through differentiation into hepatic-like cells.

Autor:	Feretis T; 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece.; Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, Greece., Katselis C; 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece.; Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, Greece., Papanikolaou IG; 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece.; Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, Greece., Apostolou K; 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece.; Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, Greece., Tsikalakis S; Department of Pathology, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece., Toutouzas KG; 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece., Theodoropoulos G; 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece., Trigka EA; Department of Pathology, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece., Saetta AA; Department of Pathology, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece., Alexakis N; 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece., Konstandoulakis M; 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece., Tsarea K; Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, Greece., Karamperi M; Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, Greece., Kletsas D; Laboratory of Cell Proliferation & Ageing, Institute of Biology NCSR 'Demokritos' Athens 15310, Greece., Patsouris E; Department of Pathology, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece., Manouras A; 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece., Zografos GC; 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece., Papalois A; 1st Department of Propaedeutic Surgery, Medical School, National Kapodistrian University of Athens, Hippocratio Hospital Athens 11527, Greece.; Experimental, Educational Research Center, ELPEN Pharmaceuticals 190 09 Pikermi, Greece.; European University Cyprus, Medical School Nicosia 2404, Cyprus.
Jazyk:	angličtina
Zdroj:	American journal of stem cells [Am J Stem Cells] 2020 Jun 15; Vol. 9 (3), pp. 36-56. Date of Electronic Publication: 2020 Jun 15 (Print Publication: 2020).
Abstrakt:	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 4α (HNF4α), cytochrome P450 1A2 (CYP1A2) and α-fetoprotein (AFP) mRNA expression. Results: Immunohistochemical staining for HGF was stronger in the transplanted groups than that in the control group (P<0.001). HNF4α 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. Competing Interests: None. (AJSC Copyright © 2020.)
Databáze:	MEDLINE
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