Multipotent Stem Cells Derived from the Adult Mouse Ovary

Background and Aim: The type(s) and differentiation potential of stemcells present in the mammalian ovary are largely unknown; whileoogonial stem cells have been reported, we explored the possibilitythat multipotent stem cells may reside in the ovary and have widedifferentiation potential.Methods: Homogenates of whole mouse ovaries were sorted usingthe stem cell surface markers Sca-1 and SSEA-1/CD15. Viable doublepositivecells (3-10 μm in diameter) were evaluated immediately aftersorting and after culture using differentiation conditions. Ovarian derivedstem cells were differentiated into the three mesenchymal cell type’sadipocytes, chondrocytes, or osteocytes. The subsequent culture wasperformed in media containing BMP-4 and/or retinoic acid (RA). RA,BMP-4 or the two agents in combination, consistently stimulated germcell gene expression.Results: RA treatment strongly stimulated germline gene expression andalso the development of cells that were morphologically reminiscent ofoocytes. The germ cell genes Dazl, Ddx4, Figla, Gdf-9, Nobox, Prdm9,and Sycp-1 were all detected at low levels. Remarkably, treatment withBMP-4 alone significantly increased protein expression of the granulosacell product Anti-müllerian hormone (AMH).Conclusion: We have shown that an inclusive isolation protocol results inthe consistent derivation of multipotent stem cells from the adult ovary;these cells can be differentiated towards the germ cell fate (RA alone),somatic ovarian cell fate as indicated by AMH production (BMP-4 alone), or classical mesenchymal cell types. Taken together these data suggestthe presence of multipotent mesenchymal stem cells in the murine ovary

Keywords:

Stem Cells , Ovary , BMP-4 , Retinoic Acid , Multipotent