In vitro derivation of germ cells from embryonic stem cells

Ko, Kinarm; Huebner, Karin; Mueller-Keuker, Jeanine; Schoeler, Hans Robert

doi:10.2741/3605

Cited by 14 publications

(10 citation statements)

References 62 publications

(99 reference statements)

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“…n the past decades, the potential of stem cells to differentiate into female germ cells has been demonstrated and reported for embryonic stem cells (reviewed in Ko et al [1]) and somatic stem cells [2][3][4][5][6]. In an ovarian follicle, the oocyte is surrounded by cumulus cells and the follicular wall is composed of granulosa and theca cells.…”

mentioning

confidence: 99%

Ovarian-Cell-Like Cells from Skin Stem Cells Restored Estradiol Production and Estrus Cycling in Ovariectomized Mice

Park

Pan²,

Toms³

et al. 2014

Stem Cells and Development

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Reduction of estradiol production and high serum concentrations of follicular stimulating hormone (FSH) are endocrine disorders associated with premature ovarian failure. Here, we report that transplantation of ovarianlike cells differentiated from stem cells restored endogenous serum estradiol levels. Stem cells were isolated from postnatal mouse skin and differentiated into ovarian-cell-like cells that are consistent with female germ, and ovarian follicle somatic cells. The ovarian-cell-like cells were transplanted into ovariectomized mice (Cell Trans), whereas control mice were subjected to bilateral ovariectomies without cell transplantation (OVX). Using vaginal cytology analysis, it was revealed that in 13 out of 19 Cell Trans mice, estrus cycles were restored around 8 weeks after cell transplantation and were maintained until 16 weeks post-transplantation, whereas in the OVX group, all mice were arrested at metestrus/diestrus of the estrus cycle. The uterine weight in the Cell Trans group was similar to sham operation mice (Sham OP), while severe uterine atrophy and a decreased uterine weight were observed in the OVX group. Histologically, ectopic follicle-like structures and blood vessels were found within and around the transplants. At 12-14 weeks after cell transplantation, mean serum estradiol level in Cell Trans mice (178.0 -35 pg/mL) was comparable to that of the Sham OP group (188.9 -29 pg/mL), whereas it was lower in the OVX group (59.0 -4 pg/mL). Serum FSH concentration increased in the OVX group (1.62 -0.32 ng/mL) compared with the Sham OP group (0.39 -0.34 ng/mL). Cell Trans mice had a similar FSH level (0.94 -0.23 ng/mL; P < 0.05) to Sham OP mice. Our results suggest that ovarian somatic cells differentiated from stem cells are functional in vivo. In addition to providing insights into the function of ovarian somatic cells derived from stem cells, our study may offer potential therapeutic means for patients with hypo-estradiol levels like those encountered in premature ovarian failure.

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mentioning

confidence: 99%

Ovarian-Cell-Like Cells from Skin Stem Cells Restored Estradiol Production and Estrus Cycling in Ovariectomized Mice

Park

Pan²,

Toms³

et al. 2014

Stem Cells and Development

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“…Making viable spermatozoa and spermatids in vitro from patient-specific PSCs, either iPSCs or SCNT-ESCs, in humans and other primates has many biomedical justifications even though the endeavour is fraught with experimental and bioethical challenges (for reviews, see Daley 2007; Ko et al . 2010; Lokman and Moore 2010; Easley et al .…”

Section: Spermatogenesis In Vitro From Pscs: Of Mice and Manmentioning

confidence: 99%

Gamete derivation from embryonic stem cells, induced pluripotent stem cells or somatic cell nuclear transfer-derived embryonic stem cells: state of the art

Easley

Simerly

Schatten

2015

Reprod. Fertil. Dev.

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Generating gametes from pluripotent stem cells (PSCs) has many scientific justifications and several biomedical rationales. Here, we consider several strategies for deriving gametes from PSCs from mice and primates (human and non-human) and their anticipated strengths, challenges and limitations. Although the ‘Weismann barrier’, which separates the mortal somatic cell lineages from the potentially immortal germline, has long existed, breakthroughs first in mice and now in humans are artificially creating germ cells from somatic cells. Spermatozoa with full reproductive viability establishing multiple generations of seemingly normal offspring have been reported in mice and, in humans, haploid spermatids with correct parent-of-origin imprints have been obtained. Similar progress with making oocytes has been published using mouse PSCs differentiated in vitro into primordial germ cells, which are then cultured after xenografting reconstructed artificial ovaries. Progress in making human oocytes artificially is proving challenging. The usefulness of these artificial gametes, from assessing environmental exposure toxicity to optimising medical treatments to prevent negative off-target effects on fertility, may prove invaluable, as may basic discoveries on the fundamental mechanisms of gametogenesis.

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“…Recent evidence reported by several independent groups has shown the ability of human, non-human primate and mouse pluripotent stem cells to differentiate into primordial germ cells (Buaas et al , 2004, Eguizabal et al , 2011, Geijsen et al , 2004, Kee et al , 2009, Kee et al , 2006, Ko et al , 2010, Nayernia et al , 2006, Panula et al , 2011, Park et al , 2009, Teramura et al , 2007, Tilgner et al , 2008, Toyooka et al , 2003, Yamauchi et al , 2009, Hayashi et al , 2011), precursor cells that contribute to gametogenesis in both males and females. Studies with mouse embryonic stem cells have even shown the ability to make functional spermatozoa (Nayernia et al , 2006, Zhao et al , 2010).…”

Section: Pluripotent Stem Cell Treatment Optionsmentioning

confidence: 99%

Stem cell therapeutic possibilities: future therapeutic options for male-factor and female-factor infertility?

Easley

Simerly

Schatten

2013

Reproductive BioMedicine Online

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Recent advances in assisted reproduction treatment have enabled some couples with severe infertility issues to conceive, but the methods are not successful in all cases. Notwithstanding the significant financial burden of assisted reproduction treatment, the emotional scars from an inability to conceive a child enacts a greater toll on affected couples. While methods have circumvented some root causes for male and female infertility, often the underlying causes cannot be treated, thus true cures for restoring a patient’s fertility are limited. Furthermore, the procedures are only available if the affected patients are able to produce gametes. Patients rendered sterile by medical interventions, exposure to toxicants or genetic causes are unable to utilize assisted reproduction to conceive a child – and often resort to donors, where permitted. Stem cells represent a future potential avenue for allowing these sterile patients to produce offspring. Advances in stem cell biology indicate that stem cell replacement therapies or in-vitro differentiation may be on the horizon to treat and could cure male and female infertility, although significant challenges need to be met before this technology can reach clinical practice. This article discusses these advances and describes the impact that these advances may have on treating infertility.

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In vitro derivation of germ cells from embryonic stem cells

Cited by 14 publications

References 62 publications

Ovarian-Cell-Like Cells from Skin Stem Cells Restored Estradiol Production and Estrus Cycling in Ovariectomized Mice

Ovarian-Cell-Like Cells from Skin Stem Cells Restored Estradiol Production and Estrus Cycling in Ovariectomized Mice

Gamete derivation from embryonic stem cells, induced pluripotent stem cells or somatic cell nuclear transfer-derived embryonic stem cells: state of the art

Stem cell therapeutic possibilities: future therapeutic options for male-factor and female-factor infertility?

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