Bioengineering in vitro models of embryonic development

Abstract

Stem cell-based in vitro models of embryonic development have been established over the last decade. Such model systems recapitulate aspects of gametogenesis, early embryonic development, or organogenesis. They enable experimental approaches that have not been possible previously and have the potential to greatly reduce the number of animals required for research. However, each model system has its own limitations, with certain aspects, such as morphogenesis and spatiotemporal control of cell fate decisions, diverging from the in vivo counterpart. Targeted bioengineering approaches to provide defined instructive external signals or to modulate internal cellular signals could overcome some of these limitations. Here, we present the latest technical developments and discuss how bioengineering can further advance the optimization and external control of stem cell-based embryo-like structures (ELSs). In vitro models combined with sophisticated bioengineering tools will enable an even more in-depth analysis of embryonic development in the future.

Sculpting with stem cells: how models of embryo development take shape

“…Overall, bridging local and global scales in stembryos is an exciting and much-needed research direction that builds on molecular biology, engineering and physics ( Gritti et al, 2021 ; Gupta et al, 2021 ; Schauer and Heisenberg, 2021 ; Torregrosa and Garcia-Ojalvo, 2021 preprint). It is, however, important to recognise the limitations and the underlying assumptions of existing techniques.…”

Signalling dynamics in embryonic development

“…With new technological developments, the mechanistic investigation of the role of signalling dynamics becomes amenable. (1) In vitro models of embryonic development and adult tissue homeostasis, including stem cell-based embryo-like structures and organoid models, that can be generated in high numbers, enable the study of signalling dynamics in accessible and simplified systems [228,229]. (2) Signalling reporters allow the spatiotemporally resolved quantification of signalling dynamics.…”

Building bridges between fields: bringing together development and homeostasis

“…This allowed the in-depth analysis of required signals and intracellular processes (Vesperini et al, 2021). Collective cell migration and cell rearrangement of, for example, PGCs and cells in the small intestine could be studied in similar systems using microfluidic chips (Gupta et al, 2021;Nikolaev et al, 2020). Recapitulating these processes in vitro will allow the dissection at mechanistic and subcellular levels.…”