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Differentiation of Adult Stem Cells Derived from Bone Marrow Stroma into Leydig or Adrenocortical Cells

Department of Biochemistry (T.Y., T.M., K.Y., H.K., T.S., M.Y., T.K., Z.S., K.M.), Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Core Research for Evolutional Science and Technology (T.Y., T.M., K.Y., H.K., T.S., M.Y., T.K., Z.S., K.M.), Japan Science and Technology Agency, Saitama 332-0012, Japan; and National Research Institute for Child Health and Development (A.U.), Tokyo 157-8535, Japan

Address all correspondence and requests for reprints to: Kaoru Miyamoto, Department of Biochemistry, Faculty of Medical Sciences, University of Fukui, Shimoaizuki, Matsuoka-cho, Fukui 910-1193, Japan. E-mail: kmiyamot{at}fmsrsa.fukui-med.ac.jp.

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.

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