PMID- 32408048
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20210514
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 251
DP  - 2020 Aug
TI  - Liver sinusoidal endothelial cells promote the differentiation and survival of 
      mouse vascularised hepatobiliary organoids.
PG  - 120091
LID - S0142-9612(20)30337-9 [pii]
LID - 10.1016/j.biomaterials.2020.120091 [doi]
AB  - The structural and physiological complexity of currently available liver 
      organoids is limited, thereby reducing their relevance for drug studies, disease 
      modelling, and regenerative therapy. In this study we combined mouse liver 
      progenitor cells (LPCs) with mouse liver sinusoidal endothelial cells (LSECs) to 
      generate hepatobiliary organoids with liver-specific vasculature. Organoids 
      consisting of 5x10(3) cells were created from either LPCs, or a 1:1 combination 
      of LPC/LSECs. LPC organoids demonstrated mild hepatobiliary differentiation in 
      vitro with minimal morphological change; in contrast LPC/LSEC organoids developed 
      clusters of polygonal hepatocyte-like cells and biliary ducts over a 7 day 
      period. Hepatic (albumin, CPS1, CYP3A11) and biliary (GGT1) genes were 
      significantly upregulated in LPC/LSEC organoids compared to LPC organoids over 7 
      days, as was albumin secretion. LPC/LSEC organoids also had significantly higher 
      in vitro viability compared to LPC organoids. LPC and LPC/LSEC organoids were 
      transplanted into vascularised chambers created in Fah(-/-)/Rag2(-/-)/Il2rg(-/-) 
      mice (50 LPC organoids, containing 2.5x10(5) LPCs, and 100 LPC/LSEC organoids, 
      containing 2.5x10(5) LPCs). At 2 weeks, minimal LPCs survived in chambers with 
      LPC organoids, but robust hepatobiliary ductular tissue was present in LPC/LSEC 
      organoids. Morphometric analysis demonstrated a 115-fold increase in HNF4alpha+ cells 
      in LPC/LSEC organoid chambers (17.26 +/- 4.34 cells/mm(2) vs 
      0.15 +/- 0.15 cells/mm(2), p = 0.018), and 42-fold increase in Sox9+ cells in 
      LPC/LSEC organoid chambers (28.29 +/- 6.05 cells/mm(2) vs 0.67 +/- 0.67 cells/mm(2), 
      p = 0.011). This study presents a novel method to develop vascularised 
      hepatobiliary organoids, with both in vitro and in vivo results confirming that 
      incorporating LSECs with LPCs into organoids significantly increases the 
      differentiation of hepatobiliary tissue within organoids and their survival 
      post-transplantation.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Yap, Kiryu K
AU  - Yap KK
AD  - O'Brien Institute, Department of St Vincent's Institute, Victoria, Australia; 
      University of Melbourne Department of Surgery, St Vincent's Hospital Melbourne, 
      Victoria, Australia. Electronic address: kyap@svi.edu.au.
FAU - Gerrand, Yi-Wen
AU  - Gerrand YW
AD  - O'Brien Institute, Department of St Vincent's Institute, Victoria, Australia.
FAU - Dingle, Aaron M
AU  - Dingle AM
AD  - O'Brien Institute, Department of St Vincent's Institute, Victoria, Australia.
FAU - Yeoh, George C
AU  - Yeoh GC
AD  - Harry Perkins Institute of Medical Research & Centre for Medical Research, 
      University of Western Australia, Western Australia, Australia.
FAU - Morrison, Wayne A
AU  - Morrison WA
AD  - O'Brien Institute, Department of St Vincent's Institute, Victoria, Australia; 
      University of Melbourne Department of Surgery, St Vincent's Hospital Melbourne, 
      Victoria, Australia; Australian Catholic University, Victoria, Australia.
FAU - Mitchell, Geraldine M
AU  - Mitchell GM
AD  - O'Brien Institute, Department of St Vincent's Institute, Victoria, Australia; 
      University of Melbourne Department of Surgery, St Vincent's Hospital Melbourne, 
      Victoria, Australia; Australian Catholic University, Victoria, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200505
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - *Endothelial Cells
MH  - Hepatocytes
MH  - Liver
MH  - Mice
MH  - *Organoids
OTO - NOTNLM
OT  - Bio-engineering
OT  - Liver disease
OT  - Liver organoids
OT  - Liver progenitor cells
OT  - Liver sinusoidal endothelial cells
OT  - Vascularised chambers
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/05/15 06:00
MHDA- 2021/05/15 06:00
CRDT- 2020/05/15 06:00
PHST- 2019/10/14 00:00 [received]
PHST- 2020/04/15 00:00 [revised]
PHST- 2020/05/02 00:00 [accepted]
PHST- 2020/05/15 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/05/15 06:00 [entrez]
AID - S0142-9612(20)30337-9 [pii]
AID - 10.1016/j.biomaterials.2020.120091 [doi]
PST - ppublish
SO  - Biomaterials. 2020 Aug;251:120091. doi: 10.1016/j.biomaterials.2020.120091. Epub 
      2020 May 5.