급성 간부전 모델에서 지지체를 이용한 FOXA2 과발현 지방줄기세포의 치료효과

Abstract

Background and Aim: For the clinical application of stem cell therapy, functional enhancement is needed to increase survival rate and engraftment rate. The purpose of this study was to investigate the effect of stem cell FOXA2 gene overexpression using scaffold system in liver disease model. Methods: Using microporator, FOXA2 was over-expressed in adipose tissue derived stem cells (ADSCs) and cultured in poly-lactic-co-glycolic acid (PLGA) scaffold. Later, ADSCs were cultured in hepatic differentiation media for two weeks by 3-steps. For in vivo experiments, FOXA2 over-expressed ADSCs were loaded in scaffold and cultured in hepatic differentiation media and later were implanted in nude mice dorsum and acute liver injury model (thioacetamide i.p. injection). Results: FOXA2 over-expressed ADSCs more increased hepatocyte-specific gene markers (AFP, CK18, albumin), cytoplasmic glycogen storage, and cytochrome P450 activity than conventional differentiation method. In vivo experiments using nude mouse showed that after two weeks scaffold implant, the mRNA expression for AFP, CK18, CD26 and CX32 more increased in FOXA2 over-expressed ADSCs group compare to ADSCs group. FOXA2 over-expressed ADSCs using scaffold treatment group attenuated liver injury in thioacetamide induced acute liver injury model without stem cell homing. Conclusion: FOXA2 over-expression ADSCs using scaffold system enhanced hepatocyte like differentiation and attenuated acute liver damage in acute liver injury model without homing effects.