ATSC transplantation contributes to liver regeneration following paracetamol-induced acute liver injury through differentiation into hepatic-like cells.
Adipose tissue stem cells
acute liver injury
cytochrome P450 1A2
drug-induced liver injury
hepatic growth factor
hepatic nuclear factor 4
liver regeneration
α-fetoprotein
Journal
American journal of stem cells
ISSN: 2160-4150
Titre abrégé: Am J Stem Cells
Pays: United States
ID NLM: 101578936
Informations de publication
Date de publication:
2020
2020
Historique:
received:
08
04
2020
accepted:
12
05
2020
entrez:
24
7
2020
pubmed:
24
7
2020
medline:
24
7
2020
Statut:
epublish
Résumé
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. 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. 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. 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.
Types de publication
Journal Article
Langues
eng
Pagination
36-56Informations de copyright
AJSC Copyright © 2020.
Déclaration de conflit d'intérêts
None.
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