Gut Liver.  2019 Jul;13(4):450-460. 10.5009/gnl18235.

The Use of Foxa2-Overexpressing Adipose Tissue-Derived Stem Cells in a Scaffold System Attenuates Acute Liver Injury

• Chae YJ
• Jun DW
• Lee JS
• Saeed WK
• Kang HT
• Jang K
• Lee JH

• KMID: 2458529
• DOI: http://doi.org/10.5009/gnl18235

Abstract

BACKGROUND/AIMS
For the clinical application of stem cell therapy, functional enhancement is needed to increase the survival rate and the engraftment rate. The purpose of this study was to investigate functional enhancement of the paracrine effect using stem cells and hepatocyte-like cells and to minimize stem cell homing by using a scaffold system in a liver disease model.
METHODS
A microporator was used to overexpress Foxa2 in adipose tissue-derived stem cells (ADSCs), which were cultured in a poly(lactic-co-glycolic acid) (PLGA) scaffold. Later, the ADSCs were cultured in hepatic differentiation medium for 2 weeks by a 3-step method. For in vivo experiments, Foxa2-overexpressing ADSCs were loaded in the scaffold, cultured in hepatic differentiation medium and later were implanted in the dorsa of nude mice subjected to acute liver injury (thioacetamide intraperitoneal injection).
RESULTS
Foxa2-overexpressing ADSCs showed greater increases in hepatocyte-specific gene markers (alpha fetoprotein [AFP], cytokeratin 18 [CK18], and albumin), cytoplasmic glycogen storage, and cytochrome P450 expression than cells that underwent the conventional differentiation method. In vivo experiments using the nude mouse model showed that 2 weeks after scaffold implantation, the mRNA expression of AFP, CK18, dipeptidyl peptidase 4 (CD26), and connexin 32 (CX32) was higher in the Foxa2-overexpressing ADSCs group than in the ADSCs group. The Foxa2-overexpressing ADSCs scaffold treatment group showed attenuated liver injury without stem cell homing in the thioacetamide-induced acute liver injury model.
CONCLUSIONS
Foxa2-overexpressing ADSCs applied in a scaffold system enhanced hepatocyte-like differentiation and attenuated acute liver damage in an acute liver injury model without homing effects.

Keyword

Liver failure, acute; Mesenchymal stem cell; Scaffold; Foxa2

MeSH Terms

Animals
Cytochrome P-450 Enzyme System
Cytoplasm
Dipeptidyl Peptidase 4
Fetal Proteins
Glycogen
Keratin-18
Liver Diseases
Liver Failure, Acute
Liver*
Mesenchymal Stromal Cells
Methods
Mice
Mice, Nude
RNA, Messenger
Stem Cells*
Survival Rate
Cytochrome P-450 Enzyme System
Dipeptidyl Peptidase 4
Fetal Proteins
Glycogen
Keratin-18
RNA, Messenger