Analysis of placenta-derived factor-treated human iPSC-liver organoid.

Organoid derived from human induced pluripotent stem cells (hiPSC) is potentially applicable for regenerative medicine. However, the applications have been hampered by limited organoid size and function as a consequence of a lack of progenitor expansion. Here, we report the recapitulation of the in vivo progenitor expansion in hiPSC-liver organoid based on the analysis of mouse development. Visualization of blood perfusion and oxygen levels in mouse embryos revealed a transient hypoxic environment despite blood flow while hepatoblast expansion. During this specific stage, the placenta was seen to express various growth factors. Human and mouse placenta-liver interaction analysis identified various placenta-derived factors. Among them, IL1a efficiently induced the growth in hiPSC-liver organoids as well as mouse fetal livers following progenitor expansion under hypoxia. Subsequent oxygenation demonstrated that expanded progenitors by IL1a contributed to hiPSC-liver organoid size and function. Taken together, treatment of placenta-derived factor under hypoxia is a crucial organoid culture technique that efficiently induces progenitor expansion. Overall design: RNA expression profiles of HE, EC, MC derived from iPSC-organoid treated with IL1a