Banas Agnieszka, Teratani Takumi, Yamamoto Yusuke, Tokuhara Makoto, Takeshita Fumitaka, Quinn Gary, Okochi Hitoshi, Ochiya Takahiro
Section for Studies on Metastasis, National Cancer Center Research Institute 1-1, Tokyo, Japan.
Hepatology. 2007 Jul;46(1):219-28. doi: 10.1002/hep.21704.
Recent observations indicate that several stem cells can differentiate into hepatocytes; thus, cell-based therapy is a potential alternative to liver transplantation. The goal of the present study was to examine the in vitro hepatic differentiation potential of adipose tissue-derived mesenchymal stem cells (AT-MSCs). We used AT-MSCs from different age patients and found that, after incubation with specific growth factors (hepatocyte growth factor [HGF], fibroblast growth factor [FGF1], FGF4) the CD105(+) fraction of AT-MSCs exhibited high hepatic differentiation ability in an adherent monoculture condition. CD105(+) AT-MSC-derived hepatocyte-like cells revealed several liver-specific markers and functions, such as albumin production, low-density lipoprotein uptake, and ammonia detoxification. More importantly, CD105(+) AT-MSC-derived hepatocyte-like cells, after transplantation into mice incorporated into the parenchyma of the liver.
Adipose tissue is a source of multipotent stem cells that can be easily isolated, selected, and induced into mature, transplantable hepatocytes. The fact that they are easy to procure ex vivo in large numbers makes them an attractive tool for clinical studies in the context of establishing an alternative therapy for liver dysfunction.
最近的观察表明，几种干细胞可分化为肝细胞；因此，基于细胞的治疗是肝移植的一种潜在替代方法。本研究的目的是检测脂肪组织来源的间充质干细胞（AT-MSCs）在体外的肝分化潜能。我们使用了来自不同年龄患者的AT-MSCs，发现与特定生长因子（肝细胞生长因子 [HGF]、成纤维细胞生长因子 [FGF1]、FGF4）孵育后，AT-MSCs的CD105(+)部分在贴壁单培养条件下表现出高肝分化能力。CD105(+) AT-MSC来源的肝细胞样细胞显示出几种肝脏特异性标志物和功能，如白蛋白产生、低密度脂蛋白摄取和氨解毒。更重要的是，CD105(+) AT-MSC来源的肝细胞样细胞移植到小鼠体内后整合到肝脏实质中。
脂肪组织是多能干细胞的一个来源，这些干细胞可以很容易地分离、筛选并诱导分化为成熟的、可移植的肝细胞。它们易于在体外大量获取这一事实使其成为建立肝功能障碍替代疗法临床研究的一个有吸引力的工具。
