Properties of Hepatocyte-like Cell Clusters from Human Adipose Tissue-Derived Mesenchymal Stem Cells
Properties of Hepatocyte-like Cell Clusters from Human Adipose Tissue-Derived Mesenchymal Stem Cells
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DOI：
10.1089/ten.tec.2009.0208
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发表时间：
2010-08-01
影响因子：
3
通讯作者：
Matsuyama, Akifumi
中科院分区：
文献类型：
--
作者：
Okura, Hanayuki;Komoda, Hiroshi;Matsuyama, Akifumi
目前仅有少数报道描述了人脂肪组织间充质干细胞(HADMSCs)向肝细胞分化的潜能，而从包括hADMSCs在内的体细胞分化而来的肝细胞样细胞在体内的功能尚未见报道。在本研究中，我们建立了一种新的方法，利用漂浮培养法建立了一种新的功能性肝细胞样细胞团的产生方法，并诱导出了功能良好的肝细胞样细胞团，不仅在体外，而且在体内都有效地发挥了作用。通过基因表达分析、功能分析和移植到非肥胖糖尿病严重联合免疫缺陷(NOD-SCID)合并慢性肝损伤的小鼠体内，对所生成的肝细胞样细胞团进行了鉴定。生成的肝细胞样细胞团表达各种通常在成熟肝细胞上存在的基因。细胞群具有肝细胞的功能特征：表达白蛋白，分泌尿素，具有细胞色素P450活性，能摄取低密度脂蛋白，并储存糖原。将这些细胞团移植到NOD-SCID慢性肝损伤小鼠体内，可显著改善血清白蛋白和总胆红素水平。综上所述，我们建立了一种高效诱导hADMSCs分化为功能性肝细胞样细胞团的新方案。
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.