Stem cell model for early human embryo development

Stem cell model for early human embryo development
Fig. 1: Induction of human blastoids under 3D two-step condition. a Schematic of human blastoid formation. EPS cells were firstly induced to TE-like cells, and then TE-like cells were mixed with EPS cells and seeded together to AgreeWell on day 0. The aggregates further differentiated and organized into a human EPS-blastoid. b Phase-contrast images of human aggregates in the indicated days showing the formation of human blastoids from day 0 to day 6. Scale bar = 5 μm. c Derivation efficiency of human blastoids is about 1.9% that significantly lower than the developmental efficiency of human blastocysts. d Phase-contrast image of human blastoids on day 6, Scale bar = 50 μm. e Phase-contrast image of human EPS-blastoid (upper) and human blastocyst (lower). Red line indicated inner cell mass (ICM) of the structure and the outer layer cells represented trophoblast cells (TE). Scale bar = 50 μm. f–h Mean diameter (f), total cell number (g), and ICM cell ratio (h) were quantified between human EPS-blastoids and blastocyst. n = 30 EPS-blastoids, n = 30 blastocyst. Data in c, data are means ± SD (n = 12 blastoids). **P < 0.001. Data in e, data are means ± SD (n = 12 blastoids). P > 0.05. Data in f and g, data are means ± SD (n = 12 blastoids). *P < 0.05. Data in h, data are numbers (n = 40 blastoids, 40 blastocysts), **P < 0.001. Credit: DOI: 10.1038/s41421-021-00316-8

The creation of cellular structures similar to blastocysts has enabled KAUST scientists to build an in vitro model that mimics the earliest moments of human embryogenesis.

A blastocyst is the first structure to develop during embryogenesis in mammals. Formed about five days after fertilization and prior to implantation in the womb, blastocysts contain the first three cell lineages of the embryo, which are vital for and organ formation. Ethical concerns severely constrain the use of human blastocysts to investigate embryo development, which has led to limited understanding of human embryogenesis and its links to developmental defects.

"To address this considerable knowledge gap, there is a pressing need for an effective that avoids the ethical issue of destroying human ," says Ph.D. student Samhan Alsolami, who worked on the study under the supervision of KAUST's Mo Li and with co-workers across China.

The only way to create blastoids—blastocyst-like structures—is to use extended (EPS ). EPS cells have a higher developmental potential than conventional human embryonic stem cells and can become both extra-embryonic cell lineages (the placenta, for example) and form the embryo itself. The team first needed to grow the trophectoderm, an extra-embryonic lineage that surrounds the embryo.

"The trophectoderm is then combined with EPS cells in a three-dimensional culture," says Alsolami. "After about five days, the EPS-blastoids self-assemble, forming a cellular close in form and function to a human blastocyst."

Initial investigations suggested that the EPS-blastoids were similar in terms of their cellular make-up and transcriptome to human embryos that were cultured for around six to ten days. This two-step protocol, while promising, is still quite inefficient, and the team are now optimizing it.

Their new model, together with other recently established models, will provide insights into human embryogenesis and allow scientists to study disorders such as infertility.

"Our work shows that it's possible to circumvent ethical issues and construct a faithful model of early human embryogenesis purely from stem cells," says Li. "Future research based on our model could potentially inform regenerative medicine, too."

"These structures will help us probe the development of human organs and multiple other processes," adds Yang Yu at Peking University Third Hospital, Beijing, who co-led the study. "This could facilitate the generation of cells or tissues solely from stem cells to replace lost or damaged tissues."

More information: Yong Fan et al, Generation of human blastocyst-like structures from pluripotent stem cells, Cell Discovery (2021). DOI: 10.1038/s41421-021-00316-8

Citation: Stem cell model for early human embryo development (2021, September 8) retrieved 25 February 2024 from
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