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iBlastoids – The Future of Human Blastocyst Research?

Review of "Modelling human blastocysts by reprogramming fibroblasts into iBlastoids" from Nature by Stuart P. Atkinson

Recent exciting studies have reported on the development of integrated in-vitro models of mouse blastocysts – or blastoids – created by the assembly of pre-established stem cell lines [1-5] or the differentiation of extended (or expanded) pluripotent stem cells into blastocyst-like structures [6]. While these mouse blastoids lack full developmental potential, they represent a hugely valuable model of certain aspects of early development [3-6].

Recent research from the laboratory of Jose M. Polo (Monash University, Clayton, Victoria, Australia) had focused on the study of intermediate cell-types that formed during the reprogramming of human fibroblasts into induced pluripotent stem cells (iPSCs); however, the team discovered that intermediate cells formed cellular structures that underwent cavitation when aggregated. In their new study [7], the Polo team now reports these "iBlastoids" as blastocyst-like structures that model several aspects of human blastocyst biology.

Lu et al. formed their three-dimensional (3D) iBlastoids from cells expressing epiblast, primitive endodermal, and trophectodermal markers generated by reprogramming human dermal fibroblasts towards pluripotency in the presence of fibroblast medium [8]. Using the AggreWell system to support 3D cellular interactions and a medium that sustained early developmental signatures, the authors formed structures that presented blastocyst-like cavitation with the proportions and spatial organization of epiblast-, primitive endoderm-, and trophectoderm-like cells similar to that found in early human blastocysts. Subsequent single-cell transcriptomics of iBlastoids provided further evidence of the presence of important cell lineages and the overall similarity to human blastocysts.

Using an adapted in-vitro attachment assay previously used to model the peri- and early post-implantation processes in human blastocysts [9, 10] (and also considering agreed conventions/laws), the authors demonstrated that iBlastoids had the potential to model human implantation accurately; specifically, iBlastoids attached within 24 hours, increased in size, flattened, and progressed to form an outgrowth,  a process similar to that reported in human blastocysts.

Overall, the authors anticipate that iBlastoids will facilitate the study of early human development, allow an evaluation of the impact of gene mutations and toxins on early embryogenesis, and foster the development of in vitro fertilization-associated therapies. Notably, the generation of iBlastoids from somatic cells avoids the use of human embryos and represent an accessible, scalable, and tractable model system; however, the authors do note that iBlastoids should not be considered as equivalent to human blastocysts as they lack particular structures/cell layers, and we currently lack any knowledge regarding their extended developmental potential.

For more on this exciting advance in human blastocyst modeling, stay tuned to the Stem Cells Portal!


References

  1. Harrison SE, Sozen B, Christodoulou N, et al., Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro. Science 2017;356:eaal1810.
  2. Sozen B, Amadei G, Cox A, et al., Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures. Nature Cell Biology 2018;20:979-989.
  3. Rivron NC, Frias-Aldeguer J, Vrij EJ, et al., Blastocyst-like structures generated solely from stem cells. Nature 2018;557:106-111.
  4. Zhang S, Chen T, Chen N, et al., Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells. Nature Communications 2019;10:496.
  5. Sozen B, Cox AL, De Jonghe J, et al., Self-Organization of Mouse Stem Cells into an Extended Potential Blastoid. Developmental Cell 2019;51:698-712.e8.
  6. Li R, Zhong C, Yu Y, et al., Generation of Blastocyst-like Structures from Mouse Embryonic and Adult Cell Cultures. Cell 2019;179:687-702.e18.
  7. Liu X, Tan JP, Schröder J, et al., Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature 2021;591:627-632.
  8. Liu X, Ouyang JF, Rossello FJ, et al., Reprogramming roadmap reveals route to human induced trophoblast stem cells. Nature 2020;586:101-107.
  9. Shahbazi MN, Jedrusik A, Vuoristo S, et al., Self-organization of the human embryo in the absence of maternal tissues. Nature Cell Biology 2016;18:700-708.
  10. Deglincerti A, Croft GF, Pietila LN, et al., Self-organization of the in vitro attached human embryo. Nature 2016;533:251-254.