Background
Human pluripotent stem cells (hPSCs) isolated from early embryos (embryonic stem cells, hESCs) or (patient-specific) induced pluripotent stem cells (hiPSCs), constitute an unparalleled resource to create scalable and renewable supplies of human cells with the potential to transform our understanding, diagnosis, and treatment of diseases for which there are currently no cures. A unique characteristic of hPSCs is their ability to differentiate into all cell types of the human body, making patient-specific hiPSCs an excellent tool for studying a broad range of organ-specific diseases and drug discovery strategies.
In recent years, the potential of hPSCs to develop into a whole embryo, as opposed to a specific cell type or organ (organoid), has attracted much scientific interest. Research in the Netherlands is at the forefront of this field, having provided international breakthroughs in the application of PSC-derived embryo models to study the peri-implantation period (blastoids, see: Beyond the Blastocyst), and early organogenesis (gastruloids, see: GREAT). Still, these models are inadequate to study the pre-implantation period (from fertilization until blastocyst formation), as they do not model the first days of embryonic development.
Generating a model from hiPSC-derived gametes can provide a way to recapitulate the pre-implantation period. A prerequisite is to realize a multi-step protocol to differentiate PSCs into gamete-like cells, via in vitro gametogenesis (IVG). In mice, it has been shown that it is possible to generate functional (male and female) gametes that, when fertilized in vitro, can develop from pre-implantation embryos to viable fertile mice. These promising results provide a (theoretical) foundation for the development of a human embryo model that can recapitulate the period from fertilization until blastocyst formation.