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

  • Chenxia Hu
  • Lanjuan LiEmail author


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.


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



Acute liver failure


Mesenchymal stromal cell


Induced pluripotent stem cells


Embryonic stem cells


Hepatocyte-like cells


Carbon tetrachloride


Conditioned medium




Hepatic encephalopathy


International normalized ratio


Acute-on-chronic liver failure




Natural killer T


Natural killer




Tumor necrosis factor alpha


Concanavalin A






Dendritic cells


T regulatory cells


Toll-like receptor 4


Polymorphonuclear neutrophils


Indoleamine 2,3-dioxygenase


Transforming growth factor


Prostaglandin E2


Adenosine triphosphate


Alanine aminotransferase


Aspartate aminotransferase


Total bilirubin


Heme oxygenase-1


Alpha fetal protein




Vascular endothelial growth factor


High mobility group box 1 protein


Epithelial cell adhesion molecule




NF-E2-related factor 2


Superoxide dismutase


Hepatocyte growth factor


Umbilical cord–derived MSCs


IL-1 receptor antagonist


Bone marrow–derived MSCs


Concanavalin A


Umbilical cord blood–derived MSCs


Adipose-derived MSCs


iPSC-derived MSCs


Proliferating cell nuclear antigen


Stromal-derived factor


Chemokine CXC receptor 4


Zeaxanthin dipalmitate


Hydrogen dioxide






Amniotic fluid–derived MSCs


Hepatic progenitor-like


Signal transducer and activator of transcription 3


Natural killer T regulatory cells


IL-17-producing natural killer T


CM derived from MSCs cocultured with hepatocytes




CM derived from hepatocytes


Nonconditioned medium




Intercellular cell adhesion molecule


Glutathione peroxidase-1




Poly (lactic acid-glycolic acid)


Regenerated silk fibroin


Liver assist devices


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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