Embryonic stem cell-like cells established by culture of adult ovarian cells in mice

Abstract

Objective To suggest an alternative strategy for deriving histocompatible stems cells without undertaking genetic manipulation. Design Prospective approach using an animal model. Setting Stem cell and bioevaluation laboratory, Seoul National University. Animal(s) F1 (C57BL6 × DBA2) and outbred (ICR) mice. Intervention(s) Ovarian stroma cells of less than 40 μm in diameter were subcultured with fibroblast monolayer, and colony-forming cells were characterized. Main Outcome Measure(s) Stemness, genotype, and imprinted gene methylation. Result(s) Two-lines of colony-forming cells were established, which expressed markers specific for embryonic stem cells (ESC) and formed embryoid bodies and teratomas. Complete matching of microsatellite markers with the cell donor strain confirmed their establishment from ovarian tissue, and identification of both homozygotic and heterozygotic chromosomes raised the possibility of their derivation from parthenogenetic oocytes. However, the use of cells smaller than mature oocytes for primary culture, the difference in imprinted gene methylation compared with parthenogenetic ESCs, and failure to establish the ESC-like cells by primary follicle culture collectively suggested the irrelevancy to gametes. Conclusion(s) Coculture of adult ovarian cells with somatic fibroblasts can yield colony-forming cells having ESC-like activity, which may provide an alternative for establishing autologous stem cells from adults that can be obtained without genetic manipulation.

Plasticity of granulosa cells: on the crossroad of stemness and transdifferentiation potential

“…Putative stem cells were found in the adult ovarian surface epithelium of different mammals, including humans [61,[78][79][80], in mouse ovarian stroma [21] and in the theca layer [29], which surrounds the developing follicle.…”

Derivation of Histocompatible Stem Cells from Ovarian Tissue

“…12) but no colonies. We are now attempting to derive ES cell-like colony-forming cells by subculturing ovarian cells; recently reported results suggest that this attempt may be successful [78]. Since ovarian tissue contains cells derived from various embryonic tissues and isolated ovarian tissue is often contaminated with blood cells, any resulting colony-forming cells or ES cells will have to be analyzed to elucidate their origin and characteristics.…”

Retraction: Detection, Characterization, and Spontaneous Differentiation In Vitro of Very Small Embryonic-Like Putative Stem Cells in Adult Mammalian Ovary

“…There is piling evidence hinting toward the existence of PSCs within the mice ovary [12,13], which may have an origin from bone marrow [14]; 6 months' culture of adult female mice germ-line stem cells and later transplantation in busulphan treated mice ovaries result in live offspring [15]; label-retaining stem cell population in mice OSE [16]; presence of multipotent stem cells with germ line potential in postnatal mouse ovary [17], and recent derivation of 2 colony-forming cell cultures with markers similar to embryonic stem (ES) cells, embryoid bodies, and teratomas from stem cells in the ovarian stroma [18,19]. Similarly, Bukovsky and his group [20] reported the presence of bipotent progenitor cells, and Virant-Klun and group [6,21,22] reported stem cells in the adult human ovaries that develop into oocytelike, embryoid body-like, and parthenote-like structures.…”