Human blastoid from primed human embryonic stem cells

Artificial human blastoids investigate fundamentals of early embryo development using in vitro models and study the pregnancy failures and birth deficiencies, previously hindered by the need for human embryos. Recent methods on generating blastoids used human naive pluripotent stem cells, which are prone to genomic instability during in vitro culturing. We introduce a simple, robust, and scalable method for generating human blastoids from more stable, human-primed, embryonic stem cells (hESC). Using a non-cell-adhesive hydrogel, hESC aggregates received the chemophysical cellular environment and formed an asymmetric blastoid structure with a cellular distribution similar to that of a human blastocyst. The obtained blastoids also demonstrated the capability of implantation in vitro . This model will allow studies on the underlying mechanisms of human pre- and post-implantation processes, leading to assisted reproductive technology. One-Sentence Summary Blastoids were generated from human-primed embryonic stem cells using appropriate chemophysical extracellular environments. ### Competing Interest Statement Kyoto University (X.W., S.T., and K.K.) filed a patent application based on the research presented herein (WO2021/079992A1). The rest of the authors declare no competing interests.