Recent Advances in Regenerative Medicine of the Liver and Bile Duct System by Chemically Induced Liver Progenitor Cells (CLiPs) in Nagasaki Experience

Hidaka, Masaaki; Miyamoto, Daisuke; Eguchi, Susumu

doi:10.1007/978-981-99-0846-2_21-1

Masaaki Hidaka²,
Daisuke Miyamoto³ &
Susumu Eguchi³

Abstract

Liver transplantation is the only treatment for end-stage liver failure. Although the development of hepatocyte therapy is expected, hepatocyte transplantation by mature hepatocytes has limitations, and regenerative medicine using hepatocytes has a problem of liver injury due to the lack of a bile excretion mechanism. The Ochiya group has shown in 2017 significant findings regarding chemically induced liver progenitor cells (CLiPs). The chemical cocktail of molecules Y27632, A-83-01, and CHIR99021 can convert mature rodent hepatocytes into proliferative bipotent cells (hepatocytes and cholangiocytes) in vitro. In this chapter, we introduced the possibility of CLiPs from rodents and humans in regenerative medicine. In vitro, study CLiPs have maintained viability for long-term culture and passaging. The construction of liver tissue and biliary drainage systems from hepatic progenitor cells using YAC is expected to enable the development of liver regenerative medicine with a bile excretion mechanism.

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Abbreviations

Ae:: Anion exchange protein
AFP:: Alpha-fetoprotein
Aqp:: Aquaporin
BA:: Bile acid
BAL:: Bioartificial liver
BC:: Bile duct
BEC:: Biliary epithelial cells
BIM:: Biliary epithelial cell induction medium
BM:: Bone marrow
Bsep:: Bile salt export pump
CDAHFD:: Choline-deficient, L-amino acid-defined, high-fat diet
CFTR:: Cystic fibrosis transmembrane conductance regulator
CK:: Cytokeratin
CLF:: Cholyl-lysyl-fluorescein
CLiPs:: Chemically induced liver progenitor cells
CTG:: Cell tracker green
CTO:: Cell tracker orange
CYP:: Cytochrome P450
EGF:: Epidermal growth factor
EHFSs:: Engineered hepatocyte/fibroblast cell sheets
EpCAM:: Epithelial cell adhesion molecule
EPS:: Extended pluripotent stem
EPS-Heps:: Extended pluripotent stem cells-hepatocytes
ESCs:: Embryonic stem cells
FGF:: Fibroblast growth factor
G6PC:: Glucose-6-phosphatase
Ggt:: Gamma-glutamyl-transferase
Gpbar:: G protein-coupled bile acid receptor
HBV:: Hepatitis B virus
HGF:: Hepatocyte growth factor
HLCs:: Hepatocyte-like cells
HNF:: Hepatocyte nuclear factor
LPCs:: Liver progenitor-like cells
Lgr5+:: Leucine-rich repeat-containing G protein-coupled receptor 5
MCD:: Methionine- and choline-deficient
MEF:: Mouse embryonic fibroblast
MH:: Mature hepatocyte
Mrp:: Multidrug resistance-associated protein
MSCs:: Mesenchymal stem cells
NASH:: Nonalcoholic steatotic hepatitis
Oatp:: Organic anion transmembrane transport
Pept:: Peptide transporter
PHH:: Primary human hepatocytes
PSCs:: Pluripotent stem cells
SOX9:: SRY-box transcription factor 9
TGF:: Transforming growth factor
TNF:: Tumor necrosis factor

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Authors and Affiliations

Department of Digestive and General Surgery, Shimane University Faculty of Medicine, Izumo, Japan
Masaaki Hidaka
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Daisuke Miyamoto & Susumu Eguchi

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Masaaki Hidaka
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Daisuke Miyamoto
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Susumu Eguchi
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Correspondence to Masaaki Hidaka .

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Department of Basic Sciences, Sulaiman Alrajhi University, AlQaseem, Saudi Arabia
Khawaja H. Haider

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Basic Sciences Department, Sulaiman AlRajhi University, AlQaseem, Saudi Arabia
Khawaja Husnain Haider
Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, Bari, Italy
Fabio Sallustio
MIRROR-Medical Institute for Regeneration, Repairing and Organ Replacement, Interdepartmental Center, University of Bari Aldo Moro, Bari, Italy
Fabio Sallustio
University of Alberta Director Clinical Islet and Living Donor Liver Transplant Program, University of Alberta, Edmonton, Canada
A. M. James Shapiro

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Hidaka, M., Miyamoto, D., Eguchi, S. (2023). Recent Advances in Regenerative Medicine of the Liver and Bile Duct System by Chemically Induced Liver Progenitor Cells (CLiPs) in Nagasaki Experience. In: Haider, K.H. (eds) Handbook of Stem Cell Applications. Springer, Singapore. https://doi.org/10.1007/978-981-99-0846-2_21-1

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DOI: https://doi.org/10.1007/978-981-99-0846-2_21-1
Received: 03 May 2023
Accepted: 06 May 2023
Published: 07 August 2023
Publisher Name: Springer, Singapore
Print ISBN: 978-981-99-0846-2
Online ISBN: 978-981-99-0846-2
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

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