PMID- 33129508
OWN - NLM
STAT- MEDLINE
DCOM- 20210624
LR  - 20210624
IS  - 1531-5037 (Electronic)
IS  - 0022-3468 (Linking)
VI  - 56
IP  - 1
DP  - 2021 Jan
TI  - Human amniotic fluid stem cells attenuate cholangiocyte apoptosis in a bile duct 
      injury model of liver ductal organoids.
PG  - 11-16
LID - S0022-3468(20)30692-8 [pii]
LID - 10.1016/j.jpedsurg.2020.09.043 [doi]
AB  - PURPOSE: Biliary atresia (BA) is a fibro-obliterative cholangiopathy that 
      involves both extrahepatic and intrahepatic bile ducts in infants. Cholangiocyte 
      apoptosis has an influence on the fibrogenesis process of bile ducts and the 
      progression of liver fibrosis in BA. Human amniotic fluid stem cells (hAFSCs) are 
      multipotent cells that have ability to inhibit cell apoptosis. We aimed to 
      investigate whether hAFSCs have the potential to attenuate cholangiocyte 
      apoptosis and injury induced fibrogenic response in our ex vivo bile duct injury 
      model of liver ductal organoids. METHODS: The anti-apoptotic effect of hAFSCs was 
      tested in the acetaminophen-induced injury model of neonatal mouse liver ductal 
      organoids (AUP #42681) by using direct and indirect co-culture systems. Cell 
      apoptosis and proliferation were evaluated by immunofluorescent staining. 
      Expression of fibrogenic cytokines was analyzed by RT-qPCR. Data were compared 
      using one-way ANOVA with post hoc test. RESULTS: In our injury model, liver 
      ductal organoids that were treated with hAFSCs in both direct and indirect 
      co-culture systems had a significantly smaller number of apoptotic cholangiocytes 
      and decreased expression of fibrogenic cytokines, transforming growth factor 
      beta-1 (TGF-beta1) and platelet-derived growth factor-BB (PDGF-BB). Moreover, hAFSCs 
      increased cholangiocyte proliferation in injured organoids. CONCLUSION: hAFSCs 
      have the ability to protect the organoids from injury by decreasing cholangiocyte 
      apoptosis and promoting cholangiocyte proliferation. This protective ability of 
      hAFSCs leads to inhibition of the fibrogenic response in the injured organoids. 
      hAFSCs have high therapeutic potential to attenuate liver fibrogenesis in 
      cholangiopathic diseases such as BA.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Chusilp, Sinobol
AU  - Chusilp S
AD  - Division of General and Thoracic Surgery, Translational Medicine Program, The 
      Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Division of Pediatric 
      Surgery, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon 
      Kaen 40002, Thailand.
FAU - Lee, Carol
AU  - Lee C
AD  - Division of General and Thoracic Surgery, Translational Medicine Program, The 
      Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
FAU - Li, Bo
AU  - Li B
AD  - Division of General and Thoracic Surgery, Translational Medicine Program, The 
      Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
FAU - Lee, Dorothy
AU  - Lee D
AD  - Division of General and Thoracic Surgery, Translational Medicine Program, The 
      Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
FAU - Yamoto, Masaya
AU  - Yamoto M
AD  - Division of General and Thoracic Surgery, Translational Medicine Program, The 
      Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
FAU - Ganji, Niloofar
AU  - Ganji N
AD  - Division of General and Thoracic Surgery, Translational Medicine Program, The 
      Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
FAU - Vejchapipat, Paisarn
AU  - Vejchapipat P
AD  - Division of Pediatric Surgery, Department of Surgery, Faculty of Medicine, 
      Chulalongkorn University, Bangkok 10330, Thailand.
FAU - Pierro, Agostino
AU  - Pierro A
AD  - Division of General and Thoracic Surgery, Translational Medicine Program, The 
      Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. Electronic address: 
      agostino.pierro@sickkids.ca.
LA  - eng
PT  - Journal Article
DEP - 20201006
PL  - United States
TA  - J Pediatr Surg
JT  - Journal of pediatric surgery
JID - 0052631
SB  - IM
MH  - *Amniotic Fluid
MH  - Apoptosis
MH  - Bile Ducts/surgery
MH  - Humans
MH  - Liver
MH  - *Organoids
MH  - Stem Cells
OTO - NOTNLM
OT  - Amniotic fluid stem cell
OT  - Bile duct injury
OT  - Cell apoptosis
OT  - Fibrogenic cytokine
COIS- Declaration of competing interest The authors declare no conflict of interest.
EDAT- 2020/11/02 06:00
MHDA- 2021/06/25 06:00
CRDT- 2020/11/01 20:26
PHST- 2020/09/03 00:00 [received]
PHST- 2020/09/22 00:00 [accepted]
PHST- 2020/11/02 06:00 [pubmed]
PHST- 2021/06/25 06:00 [medline]
PHST- 2020/11/01 20:26 [entrez]
AID - S0022-3468(20)30692-8 [pii]
AID - 10.1016/j.jpedsurg.2020.09.043 [doi]
PST - ppublish
SO  - J Pediatr Surg. 2021 Jan;56(1):11-16. doi: 10.1016/j.jpedsurg.2020.09.043. Epub 
      2020 Oct 6.