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

Introduction

Studying early human development is crucial for understanding embryonic defects and learning developmental principles that can be applied in the differentiation of human iPSCs into relevant cells for transplantation. Such research requires large numbers of human embryos; however, justified ethical barriers make this impossible.

Background

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.

Objectives

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.

Methodology

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.

Future Directions

We will 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.

Impact

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.