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Microfluidic Platform Models Early Human Development with Human Pluripotent Stem Cells

Review of “Controlled modelling of human epiblast and amnion development using stem cells” from Nature by Stuart P. Atkinson

The study of human embryo development suffers from both technical and moral problems, leaving models based on epiblast-like human and mouse pluripotent stem cells (h/mPSCs) as an alternative focus. While recent applications of micropatterned surfaces [1, 2] and microwell structures [3, 4] that prompt multicellular self-organization in controlled environments have provided for some advances, currently existing PSC models lack the efficiency and reproducibility required for mechanistic studies.

To solve this vexing problem, researchers led by Jianping Fu (University of Michigan, Ann Arbor, MI, USA) developed a controllable microfluidics-based system for hPSC culture that recapitulates developmental events in the post-implantation human embryo [5]. Zheng et al. hope that their new platform will allow for the exploration of the extensive lineage diversification, cell-fate specification, and tissue patterning that occurs during early human embryonic development.

In this fascinating new study, the authors describe the highly controllable and scalable formation of embryo-like structures through the implementation of a microfluidic device composed of three parallel channels; a central gel channel preloaded with reduced growth factor basement membrane matrix flanked by a cell-loading channel and a chemical-induction channel. The basement membrane matrix forms concave gel pockets during gelation, thereby providing a space for hPSCs (both embryonic and induced pluripotent stem cells) to settle and form clusters.

Using this system, the team observed various crucial landmarks of epiblast and amniotic ectoderm development, including epiblast lumenogenesis and the development of the resultant pro-amniotic cavity (which occurs just after the naive-to-primed pluripotency transition), the formation of a bipolar embryonic sac, and even the specification of primordial germ cells and primitive streak cells. Furthermore, the authors highlighted the implementation of this system to explore early developmental processes by establishing the importance of amniotic ectoderm-like cells as a signaling center that triggers the onset of gastrulation-like events in hPSCs.

Overall, the authors suggest that their new advance will provide a controllable, scalable, and robust new means to study human embryology and reproduction while also assisting in the rational design of hPSCs differentiation protocols for use in both disease modeling and cell therapy.

For more on this fascinating advance, see Nature News and Nature News and Views, and, as always, stay tuned to the Stem Cells Portal!

References

  1. Warmflash A, Sorre B, Etoc F, et al., A method to recapitulate early embryonic spatial patterning in human embryonic stem cells. Nature Methods 2014;11:847-854.
  2. Xue X, Sun Y, Resto-Irizarry AM, et al., Mechanics-guided embryonic patterning of neuroectoderm tissue from human pluripotent stem cells. Nature Materials 2018;17:633-641.
  3. Beccari L, Moris N, Girgin M, et al., Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids. Nature 2018;562:272-276.
  4. Rivron NC, Frias-Aldeguer J, Vrij EJ, et al., Blastocyst-like structures generated solely from stem cells. Nature 2018;557:106-111.
  5. Zheng Y, Xue X, Shao Y, et al., Controlled modelling of human epiblast and amnion development using stem cells. Nature 2019;573:421-425.