Abstract
The spontaneous return of fertility after bone marrow transplantation or heterotopic grafting of cryopreserved ovarian cortical tissue has surprised many, and a possible link with stem cells has been proposed. We have reviewed the available literature on ovarian stem cells in adult mammalian ovaries and presented a model that proposes that the ovary harbors two distinct populations of stem cells, namely, pluripotent, quiescent, very small embryonic-like stem cells (VSELs), and slightly larger “progenitor” ovarian germ stem cells (OGSCs). Besides compromising the somatic niche, oncotherapy destroys OGSCs since, like tumor cells, they are actively dividing; however VSELs persist since they are relatively quiescent. BMT or transplanted ovarian cortical tissue may help rejuvenate the ovarian niche, which possibly supports differentiation of persisting VSELs resulting in neo-oogenesis and follicular development responsible for successful pregnancies. Postnatal oogenesis in mammalian ovary from VSELs may be exploited for fertility restoration in cancer survivors including those who were earlier deprived of gametes and/or gonadal tissue cryopreservation options.
Highlights
Stem cells hold tremendous potential and promise for regenerative medicine and have raised the hope of the public for a cure for several diseases
We have recently shown the presence of very small embryonic-like stem cells (VSELs) in ovaries which can be isolated by gentle scraping of ovarian surface epithelium (OSE) in adult rabbit, sheep, monkey, and perimenopausal women
Interpretation of published literature Several groups including our results report the presence of stem cells in the ovary surface epithelium Probably they detected the bigger ovarian germ stem cells (OGSCs) since the cells were synaptonemal complex protein 3 (SCP3)+ and mouse VASA homolog (MVH)+ Chimeric follicles suggest that the oocyte and granulosa cells do not originate from a common bipotent progenitor stem cell as suggested by Bukovsky et al [26, 61, 62] Compromised ovaries in young mice possibly mobilized VSELs from the bone marrow to enter circulation In addition to the pluripotent markers (Oct-4 and Nanog), the mobilized VSELs expressed germ cell specific markers
Summary
Stem cells hold tremendous potential and promise for regenerative medicine and have raised the hope of the public for a cure for several diseases. The other challenge involves establishing protocols to achieve robust and functional oocyte differentiation from embryonic stem cells, and at present this remains a highly inefficient process. Another fast expanding area is the presence of stem cells in adult mammalian ovaries. OCT-4 positive pluripotent very small embryonic-like stem cells (VSELs) have been reported in various adult somatic tissues including bone marrow and cord blood in mice as well as humans [11,12,13]. We recently reported nuclear OCT-4A positive VSELs in adult human and mice testis [19, 20] These cells possibly undergo asymmetric cell division to give rise to slightly bigger Adark spermatogonial stem cells (SSCs), which have cytoplasmic OCT-4B. OCT-4 continues to be expressed in growing follicles, since it is a maternally inherited gene but this will not be elaborated further as it is beyond the scope of this paper
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