Towards Artificial Human Embryoid Models: Engineered and Synthetic Platforms for Ex Utero Mammalian Embryogenesis (ExUteroEmbryogenesis)

Framework: Horizon Europe — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Consolidator grants
Action type: ERC actions
Panel: Prevention,  Diagnosis and T reatment of Human Diseases
Panel description: Medical technologies  and tools for prevention, diagnosis and treatment of human diseases, therapeutic approaches and interventions , pharmacology, preventative  medicine, epidemiology and public health , digital medicine
Countries involved: Israel
Call: ERC CONSOLIDATOR GRANTS (ERC-2022-COG, 2022)
Start date: 2023-06-01
End date: 2028-05-31
Duration (months): 60.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: SIGNED

Studying early human development is crucial for understanding embryonic defects and learning developmental principles that can be applied in differentiation of human iPSCs into relevant cells for transplantation. Such research requires large numbers of human embryos, however justified ethical barriers makes this impossible. Since the mouse has been a “guiding compass” for all revolutionary technologies applied with human pluripotent stem cells, here we seek to develop biotechnologies in mice, rabbits and non-human primates (NHP) that will likely enable in the future, conceptually and technologically, circumventing this problem in humans. A two-pronged biotechnological platform development will be pursued: 1)Engineering devices that enable ex utero culture of mammalian embryos from pre-implantation until complete organogenesis 2)Establishing platforms in which in vitro expanded stem cells can be coaxed to generate synthetic embryo-like structures (embryoids), that can self-organize and be grown in the latter developed ex utero embryogenesis devices, to yield structures with both embryonic and extra-embryonic compartments, that capture advanced embryonic patterns. Motivated by our recently devised platform that allows natural mouse embryogenesis from post-implantation until organogenesis ex utero, we now aim to develop and validate biotechnological platforms that capture entire stages of development from pre-implantation until completion of organogenesis in natural mouse and rabbit embryos ex utero, and transform this knowledge to engineer advanced synthetic embryoids from in vitro expanded mouse, rabbit and NHP stem cell populations. We will utilize in-house engineered devices, stem cell-based models, cutting-edge gene editing, microscopy, optogenetics and single cell biology. Our work will establish novel platforms for generating advanced self-organizing embryoids ex utero, that can be used for stem cell differentiation, drug screening and disease modeling.

Keywords: stem cells,induced pluripotent stem cells ipscs,embryogenesis,ex utero embryogenesis,human ips disease modeling,synthetic embryos,artificial embryos,optogenetics,embryonic stem cells,transgenics,tetraploid complementation and micro injections,chimeric animals,stem cell programming and reprogramming,pluripotency,trophoblast stem cells tscs,primitive endoderm cells pre and xen cells,blastocyst