Hepatogenic differentiation from human adipose-derived stem cells and application for mouse acute liver injury

Abstract

Adipose-derived stem cells (ADSCs) derived from adipose tissue have the capacity to differentiate into endodermal, mesoderm, and ectodermal cell lineages in vitro, which are an ideal engraft in tissue-engineered repair. In this study, human ADSCs were isolated from subcutaneous fat. The markers of ADSCs, CD13, CD71, CD73, CD90, CD105, CD166, CYP3A4, and ALB were detected by immunofluorescence assays. Human ADSCs were cultured in a specific hepatogenesis differentiation medium containing HGF, bFGF, nicotinamide, ITS, and oncostatin M for hepatogenic differentiation. The hepatocyte markers were analyzed using immunofluorescence and real-time PCR after dramatic changes in morphology. Hepatocytes derived from ADSCs or ADSCs were transplanted into the mice of liver injury for observation cells colonization and therapy in liver tissue. The result demonstrated that human ADSCs were positive for the CD13, CD71, CD73, CD90, CD105, and CD166 but negative for hepatocyte markers, ALB and CYP3A4. After hepatogenic differentiation, the hepatocytes were positive for liver special markers, gene expression level showed a time-lapse increase with induction time. Human ADSCs or ADSCs-derived hepatocyte injected into the vein could improve liver function repair and functionally rescue the CCl-treated mice with liver injury, but the ADSCs transplantation was better than ADSCs-derived hepatocyte transplantation. In conclusion, our research shows that a population of hepatocyte can be specifically generated from human ADSCs and that cells may allow for participation in tissue-repair.

Therapeutic efficiency of human amniotic epithelial stem cell-derived functional hepatocyte-like cells in mice with acute hepatic failure

“…In addition, Zhou et al demonstrated that intravenous transplantation of hepatocyte-like cells from umbilical cord-derived MSCs into nude mice with CCl 4 -induced fulminant liver failure and acute liver injury not only improved serum parameters and the alternations of liver histology, but also improved survival rate of mice in severe hepatic failure [ 44 ]. There are also many other papers demonstrated that delivery of hepatocyte-like cells through intravenous injection was safe and effective [ 45 – 47 ]. To our knowledge, no attempts have so far been made to determine whether the hAESC-derived HLCs have the ability to improve liver function and rescue the acute hepatic failure mice.…”

Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases

“…However, there is a debate concerning the use of ADMSCs and HLCs in vivo. As Guo et al demonstrated, transplantation of ADMSCs and HLCs improved liver function and rescued CCl 4 -treated mice with liver injury, but ADMSC transplantation improved liver functions more effectively than transplantation of HLCs [76]. HLCs significantly restored liver function and prolonged the survival of mice with CCl 4 -induced ALF by engraftment into the injured liver, but infusion of the liver with primary hepatocytes was not effective [66].…”

Mechanisms Underlying Cell Therapy in Liver Fibrosis: An Overview

“…In other research, human ADSC-derived hepatocytes transplanted in a mouse model of liver fibrosis demonstrated improved serum levels of liver injury biochemical markers. However, non-differentiated ADSCs exhibited better results with a more accentuated decrease of ALT and AST three weeks after transplantation in comparison to ADSC-derived hepatocytes [143]. A divergent study showed that liver-injured rats who received ADSC-derived hepatocytes had better levels of serological markers (albumin, ALT, bilirubin, and alkaline phosphatase), increased levels of hepatic genes (albumin, alpha-fetoprotein, cytokeratin18, and HNF), and better cell homing than liver-injured rats who received undifferentiated ADSCs [141].…”