How important is differentiation in the therapeutic effect of mesenchymal stromal cells in liver disease?
OBJECTIVE
The protocols for differentiation of hepatocyte-like cells (HLCs) from mesenchymal stromal cells (MSCs) have been well established. Previous data have shown that MSCs and their derived HLCs were able to engraft injured liver and alleviate injuries induced by carbon tetrachloride. The goal of the current study was to determine the differences of MSCs and their derived HLCs in terms of therapeutic functions in liver diseases.


METHODS
After hepatic differentiation of umbilical cord-derived MSCs in vitro, we detected both MSC and HLC expressions of adhesion molecules and chemokine receptor CXCR4 by flow cytometry; immunosuppressive potential and hepatocyte growth factor expression were determined by means of enzyme-linked immunosorbent assay. We compared the therapeutic effect for fulminant hepatic failure in a mouse model.


RESULTS
MSC-derived-HLCs expressed lower levels of hepatocyte growth factor, accompanied by impaired immunosuppression in comparison with MSCs. Furthermore, undifferentiated MSCs showed rescuing potentials superior to those in HLCs for the treatment of fulminant hepatic failure.


CONCLUSIONS
After differentiation, HLCs lost several major properties in comparison with undifferentiated MSCs, which are beneficial for their application in liver diseases. Undifferentiated MSCs may be more appropriate than are HLCs for the treatment of liver diseases.
Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China.
Hanyu
H
Wang
Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China.
Tingting
T
Zhao
Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China.
Fang
F
Xu
Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China.
Yan
Y
Li
Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China; Beijing Alliancells-PuRui Bioscience Co, Ltd, Beijing, China; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Mingyuan
M
Wu
Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China.
Delin
D
Zhu
Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China; University of Florida, Department of Medicine, Gainesville, Florida, USA.
Xiuli
X
Cong
Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China. Electronic address: andyliuliu2001@aliyun.com.
Yongjun
Y
Liu
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017114:Liver Failure, Acute / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019718:Receptors, CXCR4 / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology
C527276:CXCR4 protein, human; D015815:Cell Adhesion Molecules; D019718:Receptors, CXCR4; D017228:Hepatocyte Growth Factor; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
cytotherapy; differentiation; liver diseases; mesenchymal stromal cells