Successful regeneration of ovarian tissue from mouse pluripotent stem cells

For the first time globally, Professor Katsuhiko Hayashi and Assistant Professor Takashi Yoshino of the Graduate School of Medical Sciences at Kyushu University, as well as Senior Researcher Takahiro Suzuki of the Riken Center for Integrative Medical Sciences, successfully reconstituted fetal ovarian somatic cell-like cells (FOSLCs) from mouse ES cells, from which functional eggs could be produced.

Previously, primordial germ cells were differentiated from induced pluripotent stem (iPS) and embryonic stem (ES) cells in various animal species; however, ovaries taken from the fetus were needed to turn them into eggs. Overcoming this issue, the research group demonstrated that eggs could be produced using only ES cells, with 11 individuals being born from 212 ES cell-derived eggs. Professor Hayashi says, "We have successfully produced eggs even with iPS cells, and we believe that we can basically apply the same strategy for other animal species. Clarification of intrafollicular cell-cell interactions will lead to the understanding of the cause of infertility and the development of therapeutic methods. In addition, there are only two endangered white rhinos in the world, and we may be able to increase their population by applying this technology." These findings were published in Science.

The research group identified the pathway inducing differentiation into FOSLCs by analyzing gene expression in detail for each stage of differentiation from the epiblast to intermediate mesoderm, early gonadal ridge, and gonad and by testing different types and amounts of reagents needed to be added to achieve such gene expression. They generated eggs using FOSLCs produced from ES cells and primordial germ cells. The developmental process of these generated cells was highly similar to that in the living body, and mice were generated by fertilization from the obtained eggs. These mice grew into reproductive adults.

Professor Hayashi says, "Led by Assistant Professor Yoshino, we achieved the results through repeated trial and error. The ovaries in the body maintain follicles for 40 years. We plan to work on understanding how such a function is achieved and on reconstructing ovarian organs with three-dimensional structures, including blood vessels and nerves."