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Improvement of mesenchymal stromal cells and their derivatives for treating acute liver failure

  • Chenxia Hu
  • Lanjuan LiEmail author
Review
  • 16 Downloads

Abstract

After the death of large numbers of cells in liver tissue is triggered by various hepatotoxic factors, intimidating and life-threatening acute liver failure (ALF) can develop with high mortality and expensive costs. Although liver transplantation and hepatocyte transplantation have become substitutes for improving liver regeneration, their applications are inhibited by scarce tissue and cell resources. Therefore, the transplantation of mesenchymal stromal cells (MSCs) and their derivatives including hepatocyte-like cells (HLCs), conditioned medium (CM), and exosomes (Ex) can help alleviate liver injury in ALF individuals or animal models via engraftment into liver tissue, hepatogenic differentiation, the promotion of host hepatocyte proliferation, the secretion of anti-inflammatory factors and antioxidants, and the enhancement of liver regeneration in vivo. In addition, biomaterial scaffolds protect MSCs against a harsh microenvironment in vitro and in vivo, in addition to providing physical and directional support for liver regeneration. In this review, we aimed to discuss the underlying mechanisms and therapeutic effects of MSCs and their derivatives on rescuing ALF animal models according to current studies. Further breakthroughs are required to establish safer, more stable, and more effective stem cell–based therapy in regenerative medicine for repairing liver injury, thus reducing the morbidity and mortality of ALF in the near future.

Keywords

Acute liver failure Mesenchymal stromal cell Hepatocyte-like cell Conditioned medium Exosomes 

Abbreviations

ALF

Acute liver failure

MSC

Mesenchymal stromal cell

iPSCs

Induced pluripotent stem cells

ESCs

Embryonic stem cells

HLCs

Hepatocyte-like cells

CCl4

Carbon tetrachloride

CM

Conditioned medium

Ex

Exosomes

HE

Hepatic encephalopathy

INR

International normalized ratio

ACLF

Acute-on-chronic liver failure

APAP

Acetaminophen

NKT

Natural killer T

NK

Natural killer

IFN-γ

Interferon-gamma

TNF-α

Tumor necrosis factor alpha

ConA

Concanavalin A

α-GalCer

Alpha-galactosylceramide

LPS

Lipopolysaccharide

DCs

Dendritic cells

Tregs

T regulatory cells

TLR4

Toll-like receptor 4

PMNs

Polymorphonuclear neutrophils

IDO

Indoleamine 2,3-dioxygenase

TGF

Transforming growth factor

PGE2

Prostaglandin E2

ATP

Adenosine triphosphate

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

TBIL

Total bilirubin

HO-1

Heme oxygenase-1

AFP

Alpha fetal protein

CK

Cytokeratin

VEGF

Vascular endothelial growth factor

HMGB1

High mobility group box 1 protein

EpCAM

Epithelial cell adhesion molecule

GSH

Glutathione

Nrf2

NF-E2-related factor 2

SOD

Superoxide dismutase

HGF

Hepatocyte growth factor

UCMSCs

Umbilical cord–derived MSCs

IL-1Ra

IL-1 receptor antagonist

BMMSCs

Bone marrow–derived MSCs

ConA

Concanavalin A

UCB-MSCs

Umbilical cord blood–derived MSCs

ADMSCs

Adipose-derived MSCs

iPSC-MSCs

iPSC-derived MSCs

PCNA

Proliferating cell nuclear antigen

SDF

Stromal-derived factor

CXCR4

Chemokine CXC receptor 4

ZD

Zeaxanthin dipalmitate

H2O2

Hydrogen dioxide

miR-210

MicroRNA-210

CAT

Catalase

AF-MSCs

Amniotic fluid–derived MSCs

HPL

Hepatic progenitor-like

STAT3

Signal transducer and activator of transcription 3

NKTregs

Natural killer T regulatory cells

NKT17

IL-17-producing natural killer T

MSC-H-CM

CM derived from MSCs cocultured with hepatocytes

D-GalN

D-galactosamine

H-CM

CM derived from hepatocytes

NCM

Nonconditioned medium

TAA

Thioacetamide

ICAM

Intercellular cell adhesion molecule

GPX1

Glutathione peroxidase-1

PG

Prostaglandin

PLGA

Poly (lactic acid-glycolic acid)

RSF

Regenerated silk fibroin

LADs

Liver assist devices

Notes

Funding information

This work was supported by the National Natural Science Foundation of China (No. 81700553), the China Postdoctoral Science Foundation (No. 2017 M183789), the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (No. 81121002), and the Independent Fund of State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine, First Affiliated HospitalZhejiang UniversityZhejiangPeople’s Republic of China

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