Starting out with ESCs and iPSCs from female mice, they tinkered with a few genes to induce epiblast-like cells (epiLCs) and then PGCLCs. They then aggregated those cells with embryonic gonadal somatic cells, which support the development of germ cells, to create "reconstituted ovaries" in vitro. The PGCLCs proliferated well, progressing similarly to PGCs in embryonic ovaries, and showed meiotic potential.
Next, they transplanted reconstituted ovaries into living mice to encourage oogenesis. After 4 weeks and 4 days, the ovaries showed clear signs of producing oocytes. Histological sections revealed that donor cells contributed to oocyte-like cells, and that almost all matured normally.
Though they did display some differences compared to wild-type oocytes, PGCLC-derived oocytes developed into two-cell embryos with similar efficiency to those from other sources. And when the embryos were transferred to foster mothers, the Japanese team reported the production of pups that grew into seemingly normal adult mice.
That breakthrough could have implications for the treatment of infertility in women, noted Reijo Pera. “Obviously, it has importance if it can be translated to humans, because the oocyte is in very short supply in many women,” she said.
Albertini was more cautious. “This is a major accomplishment for the basic scientist,” he said. “We could use this technique to generate models that could be very useful for indirectly addressing questions relevant to human biology. And it will expand the repertoire of utility for mouse models in the field of infertility treatments. But I don’t think it will have an immediate impact in terms of treating human infertility.”
He pointed out that the properties of mouse and human stem cells are very different, and that we simply don’t yet have the same knowledge of human cells. “The plasticity and utility of mouse ESCs has been very difficult to replicate with human ESCs, for example, so moving cells along a particular pathway of differentiation, in this case toward oogenesis, is going to be a lot more difficult with human stem cells.
Starting out with ESCs and iPSCs from female mice, they tinkered with a few genes to induce epiblast-like cells (epiLCs) and then PGCLCs. They then aggregated those cells with embryonic gonadal somatic cells, which support the development of germ cells, to create "reconstituted ovaries" in vitro. The PGCLCs proliferated well, progressing similarly to PGCs in embryonic ovaries, and showed meiotic potential.
Next, they transplanted reconstituted ovaries into living mice to encourage oogenesis. After 4 weeks and 4 days, the ovaries showed clear signs of producing oocytes. Histological sections revealed that donor cells contributed to oocyte-like cells, and that almost all matured normally.
Though they did display some differences compared to wild-type oocytes, PGCLC-derived oocytes developed into two-cell embryos with similar efficiency to those from other sources. And when the embryos were transferred to foster mothers, the Japanese team reported the production of pups that grew into seemingly normal adult mice.
That breakthrough could have implications for the treatment of infertility in women, noted Reijo Pera. “Obviously, it has importance if it can be translated to humans, because the oocyte is in very short supply in many women,” she said.
Albertini was more cautious. “This is a major accomplishment for the basic scientist,” he said. “We could use this technique to generate models that could be very useful for indirectly addressing questions relevant to human biology. And it will expand the repertoire of utility for mouse models in the field of infertility treatments. But I don’t think it will have an immediate impact in terms of treating human infertility.”
He pointed out that the properties of mouse and human stem cells are very different, and that we simply don’t yet have the same knowledge of human cells. “The plasticity and utility of mouse ESCs has been very difficult to replicate with human ESCs, for example, so moving cells along a particular pathway of differentiation, in this case toward oogenesis, is going to be a lot more difficult with human stem cells.
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