Liver regeneration biology: Implications for liver tumour therapies

Table 4 Examples of liver decellularization-repopulation studies

First author	Yr	Liver scaffold source	Cell source & type	Repopulation route	Outcomes	Ref.
Uygun	2010	Rat	Rat hepatocytes	Portal vein	Recellularised liver grafts implanted in rats, perfused in vivo for 8 h, explanted and assessed after 24 h, demonstrating hepatocyte survival, albumin secretion, urea synthesis and cytochrome P450 expression.	Uygun 2010[127]
Zhou	2011	Mouse	Human foetal hepatocytes	Portal vein	Recellularised liver matrix implanted in mice, achieving hepatocyte survival after 6 wk, with albumin secretion and cytochrome P450 expression.	Zhou 2011[131]
Ko	2014	Pig	Murine endothelial cells, after scaffold conjugation with rat anti-mouse CD31 antibodies	Portal veinHepatic arteryInferior vena cava	Recellularised liver grafts implanted in pigs, demonstrating good blood flow and patency throughout vascular network over 24 h after transplantation.	Ko 2015[130]
Navarro-Tableros	2015	Rat	Human liver stem-like cells	Portal vein	Loss of embryonic markers, expression of albumin, lactate dehydrogenase and cytochrome P450 subtypes. Production of urea and nitrogen.	Navarro-Tableros 2015[133]
Ogiso	2016	Rat	Mouse hepatocytes	Biliary tree; Portal vein	(1) > 80% of cells seeded via biliary tree entered the parenchyma; (2) Approximate 20% of cells seeded via portal vein entered the parenchyma; and (3) Increased gene expression of foetal hepatocyte albumin, glucose 6-phosphatase, transferrin, cytokeratin 19, and gamma-glutamyl transpeptidase, activation of liver detoxification enzymes, formation of biliary duct-like structures.	Ogiso 2016[132] [PMID 27767181]
Verstegen	2017	Human	Human umbilical vein endothelial cells.	-	Re-endothelialisation of vascular tree, demonstrated by luminal vimentin and von Willebrand Factor/F8 staining.	Verstegen 2017[138]
Butter	2018	Rat	Rat hepatocytes	Hepatic artery and portal vein	In vitro demonstration of hepatocyte spread to all liver lobes, with proliferation, and production of aminotransferases, lactate dehydrogenase and albumin.	Butter 2018[134]
Chen	2018	Rat	Rat hepatocytes	Portal vein	None (description of materials and methods).	Chen 2018[135]
Chen	2019	Rat	Rat cholangiocytes Rat hepatocytes	Common bile duct; Portal vein	In vitro viability and function demonstrated by albumin and urea secretion, and gene expression of functional proteins.	Chen 2019[136]
Harper	2020	Rat	Rat bone marrow cells	Portal vein	Stem cells engrafted in portal, sinusoidal and hepatic vein compartments, achieving expression of endothelial cell surface markers for up to 30 d.	Harper 2020[118]
Takeishi	2020	Rat	Human hepatocytes, biliary epithelial cells, and vascular endothelial cells derived from pluripotent stem cells, mesenchymal cells, and fibroblasts.	Biliary tree; Portal vein; Central veins	Auxiliary grafts implanted in rats, achieving in vivo functionality for 4 d.	Takeishi 2020[137]