Banas Agnieszka, Teratani Takumi, Yamamoto Yusuke, Tokuhara Makoto, Takeshita Fumitaka, Osaki Mitsuhiko, Kawamata Masaki, Kato Takashi, Okochi Hitoshi, Ochiya Takahiro
Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo, Japan.
Stem Cells. 2008 Oct;26(10):2705-12. doi: 10.1634/stemcells.2008-0034. Epub 2008 Jun 5.
Mesenchymal stem cells (MSCs), largely present in the adult human body, represent an attractive tool for the establishment of a stem cell-based therapy for liver diseases. Recently, the therapeutic potential and immunomodulatory activity of MSCs have been revealed. Adipose tissue-derived mesenchymal stem cells (AT-MSCs), so-called adipose-derived stem cells or adipose stromal cells, because of their high accessibility with minimal invasiveness, are especially attractive in the context of future clinical applications. The goal of the present study was to evaluate the therapeutic potential of AT-MSCs by their transplantation into nude mice with CCl(4)-caused liver injury. We observed that after transplantation, AT-MSCs can improve liver functions, which we verified by changes in the levels of biochemical parameters. Ammonia, uric acid, glutamic-pyruvic transaminase, and glutamic-oxaloacetic transaminase concentrations returned to a nearly normal level after AT-MSC transplantation. These results raised the question of how AT-MSCs can achieve this. To discover the possible mechanisms involved in this therapeutic ability of AT-MSCs, in vitro production of cytokines and growth factors was analyzed and compared with MSCs from bone marrow (BM-MSCs) and normal human dermal fibroblasts (NHDFs). As a result we observed that AT-MSCs secrete interleukin 1 receptor alpha (IL-1Ralpha), IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein 1, nerve growth factor, and hepatocyte growth factor in a volume higher than both BM-MSCs and NHDFs. Thus, our findings suggest that AT-MSCs may account for their broad therapeutic efficacy in animal models of liver diseases and in the clinical settings for liver disease treatment. Disclosure of potential conflicts of interest is found at the end of this article.
间充质干细胞（MSCs）大量存在于成人体内，是一种颇具吸引力的工具，可用于建立基于干细胞的肝病治疗方法。最近，MSCs的治疗潜力和免疫调节活性已被揭示。脂肪组织来源的间充质干细胞（AT-MSCs），即所谓的脂肪来源干细胞或脂肪基质细胞，因其具有高度可及性且侵入性最小，在未来临床应用方面特别具有吸引力。本研究的目的是通过将AT-MSCs移植到四氯化碳诱导肝损伤的裸鼠中来评估其治疗潜力。我们观察到移植后，AT-MSCs可以改善肝功能，这通过生化参数水平的变化得到了验证。氨、尿酸、谷丙转氨酶和谷草转氨酶浓度在AT-MSCs移植后恢复到接近正常水平。这些结果引发了一个问题，即AT-MSCs如何能够实现这一点。为了发现AT-MSCs这种治疗能力所涉及的可能机制，分析了其细胞因子和生长因子的体外产生情况，并与骨髓间充质干细胞（BM-MSCs）和正常人皮肤成纤维细胞（NHDFs）进行了比较。结果我们观察到，AT-MSCs分泌白细胞介素1受体α（IL-1Rα）、IL-6、IL-8、粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、单核细胞趋化蛋白1、神经生长因子和肝细胞生长因子的量高于BM-MSCs和NHDFs。因此，我们的研究结果表明，AT-MSCs可能是其在肝病动物模型和肝病治疗临床环境中具有广泛治疗效果的原因。潜在利益冲突的披露见本文末尾。
