Differentiation of adult stem cells derived from bone marrow stroma into Leydig or adrenocortical cells.
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.
Yazawa
Takashi
T
Department of Biochemistry, Faculty of Medical Sciences, University of Fukui, Matsuoka-cho, Fukui 910-1193, Japan.
Mizutani
Tetsuya
T
Yamada
Kazuya
K
Kawata
Hiroko
H
Sekiguchi
Toshio
T
Yoshino
Miki
M
Kajitani
Takashi
T
Shou
Zhangfei
Z
Umezawa
Akihiro
A
Miyamoto
Kaoru
K
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000302:Adrenal Cortex / Q000166:cytology*; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D000242:Cyclic AMP / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007985:Leydig Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D054339:Steroidogenic Factor 1; D013256:Steroids / Q000096:biosynthesis; D017154:Stromal Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection
D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D013256:Steroids; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; C515060:steroidogenic factor 1, rat; D049452:Green Fluorescent Proteins; D000242:Cyclic AMP; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme