IFATS Collection: In Vivo Therapeutic Potential of Human Adipose Tissue Mesenchymal Stem Cells After Transplantation into Mice with Liver Injury
IFATS Collection: In Vivo Therapeutic Potential of Human Adipose Tissue Mesenchymal Stem Cells After Transplantation into Mice with Liver Injury
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DOI：
10.1634/stemcells.2008-0034
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
Ochiya, Takahiro
中科院分区：
文献类型：
--
作者：
Banas, Agnieszka;Teratani, Takumi;Ochiya, Takahiro
间充质干细胞（MSC），主要存在于成年人体，代表了一个有吸引力的工具，用于建立基于干细胞的治疗肝病。近年来，MSC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），又称脂肪来源的干细胞或脂肪基质细胞，由于其具有高可及性和低侵袭性，在未来的临床应用中特别有吸引力。本研究的目的是通过将AT-MSCs移植到CCl 4引起的肝损伤裸鼠体内来评估其治疗潜力。我们观察到移植后AT-MSCs可以改善肝功能，我们通过生化指标水平的变化验证了这一点。氨，尿酸，谷氨酰胺转氨酶，谷草转氨酶浓度恢复到接近正常水平后，AT-MSC移植。这些结果提出了AT-MSC如何实现这一目标的问题。为了发现参与AT-MSC的这种治疗能力的可能机制，分析了细胞因子和生长因子的体外产生，并与来自骨髓的MSC（BM-MSC）和正常人真皮成纤维细胞（NHDF）进行比较。结果，我们观察到AT-MSC分泌白细胞介素1受体α（IL-1 R α）、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-MSC和NHDF。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广泛治疗功效的原因。干细胞2008; 26：2705-2712
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 CCl4-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-1R alpha), 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. STEM CELLS 2008; 26: 2705-2712