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

• Published in: Gut and liver Vol. 13; no. 4; pp. 450 - 460
• Main Authors: Chae, Yeon Ji, Jun, Dae Won, Lee, Jai Sun, Saeed, Waqar Khalid, Kang, Hyeon Tae, Jang, Kiseok, Lee, Jin Ho
• Format: Journal Article
• Language: English
• Published: Korea (South) Editorial Office of Gut and Liver 15-03-2019; Gastroenterology Council for Gut and Liver; 거트앤리버 소화기연관학회협의회
• Subjects: acute; Albumins - metabolism; alpha-Fetoproteins - genetics; alpha-Fetoproteins - metabolism; Animals; Biocompatible Materials; Cell Differentiation - genetics; Cells, Cultured; Chemical and Drug Induced Liver Injury - therapy; Connexins - genetics; Cytochrome P-450 Enzyme System - metabolism; Dipeptidyl Peptidase 4 - genetics; Electroporation; foxa2; Gap Junction beta-1 Protein; Glycogen - metabolism; Hepatocyte Nuclear Factor 3-beta - genetics; Hepatocytes - metabolism; Keratin-18 - genetics; Keratin-18 - metabolism; Liver - metabolism; liver failure; mesenchymal stem cell; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells - metabolism; Mice; Mice, Nude; Original; Plasmids; Polylactic Acid-Polyglycolic Acid Copolymer; scaffold; Thioacetamide; Tissue Scaffolds; 내과학; Mesenchymal stem cell; acute; Liver failure; Scaffold; Foxa2
• ISSN: 1976-2283; 2005-1212
• DOI: 10.5009/gnl18235

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.
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
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).
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.
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.
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.