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. 2020 Feb 11;14(2):169-174.
doi: 10.1016/j.stemcr.2019.12.008. Epub 2020 Jan 16.

Toward Guidelines for Research on Human Embryo Models Formed From Stem Cells

Free PMC article

Toward Guidelines for Research on Human Embryo Models Formed From Stem Cells

Insoo Hyun et al. Stem Cell Reports. .
Free PMC article


Over the past few years, a number of research groups have reported striking progress on the generation of in vitro models from mouse and human stem cells that replicate aspects of early embryonic development. Not only do these models reproduce some key cell fate decisions but, especially in the mouse system, they also mimic the spatiotemporal arrangements of embryonic and extraembryonic tissues that are required for developmental patterning and implantation in the uterus. If such models could be developed for the early human embryo, they would have great potential benefits for understanding early human development, for biomedical science, and for reducing the use of animals and human embryos in research. However, guidelines for the ethical conduct of this line of work are at present not well defined. In this Forum article, we discuss some key aspects of this emerging area of research and provide some recommendations for its ethical oversight.


Figure 1
Figure 1
The Different Embryo Models Models of the embryo have been formed using mouse (left) and human stem cells (right) to mimic the development of (parts of) the embryo proper (orange) and the extraembryonic tissues (blue) of the conceptus (gray). Mouse models include blastoids (left, top) that resemble the pre-implantation 3.5-day-old conceptus, contain analogues of the three lineages forming the embryo proper, placenta, and yolk sac, and recapitulate aspects of the implantation into the uterus; ETX embryo models (left, middle) that resemble inner regions of the early post-implantation 6.5-day-old conceptus, contain analogues of the three lineages forming the embryo, placenta, and visceral endoderm, mimic an anteroposterior patterning, and form gastrulating-like cells; and gastruloids (left, bottom) that resemble the medial and posterior parts of the 8.5-day-old embryo proper form features of the three orthogonal axes that serve as a reference for the organization of the derivatives of the three germ layers and an appropriate distribution of the primordia-like cells. Work with human stem cells is less advanced but is on a similar trajectory. Currently, epiblast-amniotic models (right, top) recapitulate features of the formation of the amniotic cavity, epiblast-amniotic ectoderm axis, and gastrulation, while human stem cells grown on 2D micropatterns (right, bottom) model aspects of post-implantation patterning. Days 7–9 and day 14 of human development (marked in red) are important biological milestones that delineate the emergence of specific properties, such as the capacity to implant in the uterus and the formation of the primitive streak (gastrulation), respectively.

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