Cell-based therapy for acute and chronic liver failures: distinct diseases, different choices

Kai Sun; Xuqin Xie; Jing Xie; Shufan Jiao; Xiaojing Chen; Xue Zhao; Xin Wang; Lixin Wei

doi:10.1038/srep06494

Cell-based therapy for acute and chronic liver failures: distinct diseases, different choices

Sci Rep. 2014 Sep 29:4:6494. doi: 10.1038/srep06494.

Authors

Kai Sun¹, Xuqin Xie², Jing Xie³, Shufan Jiao¹, Xiaojing Chen¹, Xue Zhao¹, Xin Wang⁴, Lixin Wei⁵

Affiliations

¹ Central laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² 1] Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China [2] Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
³ Department of Gynecology, Shanghai Tianshan Hospital, Shanghai, China.
⁴ 1] The Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Huhhot, P.R.China [2] Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, MN, USA [3] Hepatoscience Incorporation, Palo Alto, CA.
⁵ 1] Central laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China [2] Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.

Abstract

Cell-based therapies (CBTs) are considered the effective approaches to treat liver failure. However, which cell type is the most suitable source of CBTs for acute liver failure (ALF) or chronic liver failure (CLF) remains unclear. To investigate this, mature hepatocytes in adult liver (adult HCs), fetal liver cells (FLCs), induced hepatic stem cells (iHepSCs) and bone marrow derived mesenchymal stromal cells (BMSCs) were used to CBTs for ConA-induced ALF and Fah-deficient induced CLF in mice. The results showed that only BMSCs remitted liver damage and rescued ALF in ConA-treated mice. In this process, BMSCs inhibited ConA-induced inflammatory response by decreasing the mRNA expressions of TNF-α, IFN-γ and FasL and increasing IL-10 mRNA expression. However, in the CLF model, not BMSCs but adult HCs transplantation lessened liver injury, recovered liver function and rescued the life of Fah-/- mice after NTBC withdrawal. Further study showed that adult HCs offered more effective liver regeneration compared to other cells in Fah-/- mice without NTBC. These results demonstrated that BMSCs and adult HCs are the optimal sources of CBTs for ConA-induced ALF and Fah-deficient induced CLF in mice, respectively. This finding deepens our understanding about how to select a proper CBT for different liver failure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / genetics
Cell- and Tissue-Based Therapy*
Concanavalin A / toxicity
End Stage Liver Disease / chemically induced
End Stage Liver Disease / pathology
End Stage Liver Disease / therapy*
Hepatocytes / transplantation
Liver Failure, Acute / chemically induced
Liver Failure, Acute / pathology
Liver Failure, Acute / therapy*
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells / cytology
Mice

Substances

Concanavalin A