Differentiation of adult stem cells derived from bone marrow stroma into Leydig or adrenocortical cells.
Differentiation of adult stem cells derived from bone marrow stroma into Leydig or adrenocortical cells.
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DOI：
10.1210/en.2006-0162
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发表时间：
2006-09
期刊：
影响因子：
4.8
通讯作者：
T. Yazawa;T. Mizutani;Kazuya Yamada;H. Kawata;T. Sekiguchi;M. Yoshino;Takashi Kajitani;Z. Shou
中科院分区：
文献类型：
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作者：
T. Yazawa;T. Mizutani;Kazuya Yamada;H. Kawata;T. Sekiguchi;M. Yoshino;Takashi Kajitani;Z. Shou
来自骨髓的成体干细胞，称为间充质干细胞或骨髓基质细胞（MSC），被定义为多能细胞，具有分化成多种中胚层细胞的能力。在这项研究中，我们研究了来自大鼠、小鼠和人类的间充质干细胞是否能够分化为类固醇生成细胞。当移植到未成熟的大鼠睾丸中时，发现贴壁的骨髓来源细胞（包括间充质干细胞）被移植并分化为与间质细胞无法区分的类固醇生成细胞。使用由类固醇生成细胞特异性基因 P450 侧链裂解酶基因 (CYP11A) 启动子驱动的绿色荧光蛋白转染分离的小鼠 MSC，用于检测体外类固醇生成细胞的产生。在体外分化过程中，发现了绿色荧光蛋白阳性细胞，其特征与Leydig细胞相似。用转录因子、类固醇生成因子-1 稳定转染小鼠 MSC，然后用 cAMP 处理，几乎重现了 Leydig 细胞的特性，包括睾酮的产生。用类固醇生成因子 1 转染人间充质干细胞也导致它们转化为类固醇生成细胞，但它们似乎是产生糖皮质激素的细胞，而不是产生睾酮的细胞。这些结果表明间充质干细胞是产生类固醇细胞的有用干细胞来源，这可能为其在细胞和基因治疗中的应用提供基础。
Adult stem cells from bone marrow, referred to as mesenchymal stem cells or marrow stromal cells (MSCs), are defined as pluripotent cells and have the ability to differentiate into multiple mesodermal cells. In this study, we investigated whether MSCs from rat, mouse, and human are able to differentiate into steroidogenic cells. When transplanted into immature rat testes, adherent marrow-derived cells (including MSCs) were found to be engrafted and differentiate into steroidogenic cells that were indistinguishable from Leydig cells. Isolated murine MSCs transfected with green fluorescence protein driven by the promoter of P450 side-chain cleaving enzyme gene (CYP11A), a steroidogenic cell-specific gene, were used to detect steroidogenic cell production in vitro. During in vitro differentiation, green fluorescence protein-positive cells, which had characteristics similar to those of Leydig cells, were found. Stable transfection of murine MSCs with a transcription factor, steroidogenic factor-1, followed by treatment with cAMP almost recapitulated the properties of Leydig cells, including the production of testosterone. Transfection of human MSCs with steroidogenic factor-1 also led to their conversion to steroidogenic cells, but they appeared to be glucocorticoid- rather than testosterone-producing cells. These results indicate that MSCs represent a useful source of stem cells for producing steroidogenic cells that may provide basis for their use in cell and gene therapy.