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Stem Cells in Liver Regeneration and Their Potential Clinical Applications

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Abstract

Stem cells constitute a population of “primitive cells” with the ability to divide indefinitely and give rise to specialized cells under special conditions. Because of these two characteristics they have received particular attention in recent decades. These cells are the primarily responsible factors for the regeneration of tissues and organs and for the healing of lesions, a feature that makes them a central key in the development of cell-based medicine, called Regenerative Medicine. The idea of wound and organ repair and body regeneration is as old as the mankind, reflecting the human desire for inhibiting aging and immortality and it is first described in the ancient Greek myth of Prometheus. It is of interest that the myth refers to liver, an organ with remarkable regenerative ability after loss of mass and function caused by liver injury or surgical resection. Over the last decade there has been an important progress in understanding liver physiology and the mechanisms underlying hepatic development and regeneration. As liver transplantation, despite its difficulties, remains the only effective therapy for advanced liver disease so far, scientific interest has nowadays been orientated towards Regenerative Medicine and the use of stem cells to repair damaged liver. This review is focused on the available literature concerning the role of stem cells in liver regeneration. It summarizes the results of studies concerning endogenous liver regeneration and stem cell experimental protocols. Moreover, this review discusses the clinical studies that have been conducted in humans so far.

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Abbreviations

2-AAF:

2-acetylaminofluorene

AFP:

Alpha fetoprotein

ALB:

Albumin

BM:

Bone marrow

BM-MSC:

Bone marrow derived mesenchymal stem cell

BM-SC:

Bone marrow stem cell

CCl4 :

Carbon tetrachloride

CK:

Cytokeratin

EB:

Embryoid body

ESC:

Embryonic stem cell

FAH:

Fumarylacetoacetate hydrolase

G-CSF:

Granulocyte colony stimulating factor

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HEV:

Hepatitis E virus

hHpSCs:

Human hepatic stem cells

HNF:

Hepatocyte nuclear factor

HNF-3β:

Hepatocyte nuclear factor 3 beta

HSC:

Hematopoietic stem cell

ICG:

Indocyanine green

iPSC:

Induced pluripotent stem cell

LIF:

Leukemia inhibiting factor

MAPC:

Multipotent adult progenitor cell

MEFC:

Mouse embryonic fibroblast cell

MMP:

Metalloproteinase

MSC:

Mesenchymal stem cell

MSC-CM:

Mesenchymal stem cell conditioned medium

NTBC:

2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC)

PH:

Partial hepatectomy

rha-FGF:

Recombinant human acidic fibroblast growth factor

rhb-FGF:

Recombinant human basic fibroblast growth factor

rHGF:

Recombinant hepatocyte growth factor

TTR:

Transthyretin

UCB:

Umbilical cord blood

UCB-HSC:

Umbilical cord blood derived hematopoietic stem cell

UCB-MSC:

Umbilical cord blood derived mesenchymal stem cell

uPA:

Urokinase plasminogen activator

γ-GT:

Gamma glutamyltransferase

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  1. Laboratory of Pharmacology, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece

    Ioannis Drosos & George Kolios

  2. Laboratory of Pharmacology, School of Medicine, Democritus University of Thrace, Dragana, Alexandroupolis, 68100, Greece

    George Kolios

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Drosos, I., Kolios, G. Stem Cells in Liver Regeneration and Their Potential Clinical Applications. Stem Cell Rev and Rep 9, 668–684 (2013). https://doi.org/10.1007/s12015-013-9437-4

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