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Current status of hepatocyte-like cell therapy from stem cells

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Abstract

Organ liver transplantation and hepatocyte transplantation are not performed to their full potential because of donor shortage, which could be resolved by identifying new donor sources for the development of hepatocyte-like cells (HLCs). HLCs have been differentiated from some stem cell sources as alternative primary hepatocytes throughout the world; however, the currently available techniques cannot differentiate HLCs to the level of normal adult primary hepatocytes. The outstanding questions are as follows: which stem cells are the best cell sources? which protocol is the best way to differentiate them into HLCs? what is the definition of differentiated HLCs? how can we enforce the function of HLCs? what is the difference between HLCs and primary hepatocytes? what are the problems with HLC transplantation? This review summarizes the current status of HLCs, focusing on stem cell sources, the differentiation protocol for HLCs, the general characterization of HLCs, the generation of more functional HLCs, comparison with primary hepatocytes, and HLCs in cell-transplantation-based liver regeneration.

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Abbreviations

HLCs:

Hepatocyte-like cells

IPSCs:

Induced pluripotent stem cells

ESCs:

Embryonic stem cells

MSCs:

Mesenchymal stem cells

HGF:

Hepatocyte growth factor

PI3K:

Phosphoinositide 3-kinase

GSK3:

Glycogen synthase kinase 3

FGF:

Fibroblast growth factors

BMP:

Bone morphogenetic proteins

DMSO:

Dimethyl sulfoxide

OsM:

Oncostatin M

Dex:

Dexamethasone

AFP:

Alpha fetoprotein

IGF-1:

Insulin-like growth factor-I

SOX17:

SRY-Box 17

HEX:

Hematopoietically expressed homeobox

HNF:

Hepatocyte nuclear factor

FOXA2:

Forkhead box A2

ALB:

Albumin

ATD:

AAT deficiency

LDLR:

Low-density lipoprotein receptor

PCSK9:

Proprotein convertase subtilisin kexin type 9

FTA:

Familial transthyretin amyloidosis

GSD1A:

Glycogen storage disease type 1a

CN1:

Crigler-Najjar syndrome type 1

PH1:

Primary hyperoxaluria-1

EBiSC:

European Bank for induced pluripotent Stem Cells

FH:

Familial hypercholesterolemia

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  1. Department of Surgery, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan

    Yu Saito, Tetsuya Ikemoto, Yuji Morine & Mitsuo Shimada

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  1. Yu Saito
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Saito, Y., Ikemoto, T., Morine, Y. et al. Current status of hepatocyte-like cell therapy from stem cells. Surg Today 51, 340–349 (2021). https://doi.org/10.1007/s00595-020-02092-6

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