Department of Somatic Stem Cell Therapy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe, Japan.
Tissue Eng Part C Methods. 2010 Aug;16(4):761-70. doi: 10.1089/ten.TEC.2009.0208.
There are only a few reports that describe the hepatocytic differentiation potential of human adipose tissue-derived mesenchymal stem cells (hADMSCs) and no reports that describe the in vivo functions of hepatocyte-like cells differentiated from somatic stem cells including hADMSCs. In this study, we established a new method for generation of functional hepatocyte-like cell clusters using floating culture method and induced functional hepatocyte-like cell clusters, which functioned effectively not only in vitro but also in vivo. The generated hepatocyte-like cell clusters were characterized by gene expression analysis, functional assays, and transplantation into non-obese diabetic severe combined immunodeficiency (NOD-SCID) mouse with chronic liver injury. The generated hepatocyte-like cell clusters expressed various genes normally found on mature hepatocytes. The cell clusters exhibited functional characteristics of hepatocytes: they expressed albumin, secreted urea, had cytochrome P450 activity, could take up low-density lipoprotein, and stored glycogen. Transplantation of these cell clusters into NOD-SCID mouse with chronic liver injury resulted in a significant improvement of serum albumin and total bilirubin levels. In summary, we established a new protocol for efficient induction of hADMSCs into functional hepatocyte-like cell clusters.
仅有少数报道描述了人脂肪组织来源的间充质干细胞（hADMSCs）的肝实质细胞分化潜能，尚无报道描述包括 hADMSCs 在内的体干细胞分化为具有功能的肝样细胞在体内的功能。在本研究中，我们建立了一种新的使用悬浮培养方法生成功能性肝样细胞簇的方法，并诱导生成了具有功能的肝样细胞簇，这些细胞不仅在体外而且在体内均能有效发挥功能。通过基因表达分析、功能测定以及将生成的肝样细胞簇移植到非肥胖型糖尿病严重联合免疫缺陷（NOD-SCID）小鼠慢性肝损伤模型中，对生成的肝样细胞簇进行了鉴定。生成的肝样细胞簇表达成熟肝细胞中常见的各种基因。细胞簇表现出肝细胞的功能特征：表达白蛋白、分泌尿素、具有细胞色素 P450 活性、能够摄取低密度脂蛋白和储存糖原。将这些细胞簇移植到慢性肝损伤的 NOD-SCID 小鼠中，可显著改善血清白蛋白和总胆红素水平。总之，我们建立了一种新的高效诱导 hADMSCs 分化为具有功能的肝样细胞簇的方案。
