人脂肪基质细胞在体外和体内向肝系的分化

Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo.

作者信息

Seo Min Jeong, Suh Su Young, Bae Yong Chan, Jung Jin Sup

机构信息

Department of Physiology, College of Medicine, Pusan National University, Pusan 602-739, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2005 Mar 4;328(1):258-64. doi: 10.1016/j.bbrc.2004.12.158.

DOI:10.1016/j.bbrc.2004.12.158

PMID:15670778

Abstract

Embryonic stem cells (ES cells), bone marrow-derived mesenchymal stem cells, umbilical cord blood-derived mesenchymal stem cells, and hepatic stem cells in liver have been known as a useful source that can induce to differentiate into hepatocytes. In this study, we examined whether human adipose tissue-derived stromal cells (hADSC) can differentiate into hepatic lineage in vitro. hADSC, that were induced to differentiate into hepatocyte-like cells by the treatment of HGF and OSM, had morphology similar to hepatocytes. Addition of DMSO enhanced differentiation into hepatocytes. RT-PCR and immunocytochemical analysis showed that hADSC express albumin and alpha-fetoprotein during differentiation. Differentiated hADSC showed LDL uptake and production of urea. Additionally, transplanted hADSC to CCl4-injured SCID mouse model were able to be differentiated into hepatocytes and they expressed albumin in vivo. Mesenchymal stem cells isolated from human adipose tissue are immunocompatible and are easily isolated. Therefore, hADSC may become an alternative source to hepatocyte regeneration or liver cell transplantation.

摘要

胚胎干细胞（ES细胞）、骨髓来源的间充质干细胞、脐带血来源的间充质干细胞以及肝脏中的肝干细胞，已被认为是可诱导分化为肝细胞的有用细胞来源。在本研究中，我们检测了人脂肪组织来源的基质细胞（hADSC）在体外是否能分化为肝系细胞。经HGF和OSM处理诱导分化为类肝细胞的hADSC，其形态与肝细胞相似。添加二甲基亚砜（DMSO）可增强向肝细胞的分化。逆转录聚合酶链反应（RT-PCR）和免疫细胞化学分析表明，hADSC在分化过程中表达白蛋白和甲胎蛋白。分化后的hADSC表现出低密度脂蛋白（LDL）摄取和尿素生成。此外，将hADSC移植到四氯化碳损伤的重症联合免疫缺陷（SCID）小鼠模型中，它们能够在体内分化为肝细胞并表达白蛋白。从人脂肪组织分离的间充质干细胞具有免疫相容性且易于分离。因此，hADSC可能成为肝细胞再生或肝细胞移植的替代细胞来源。