Three-dimensional human placenta-like bud synthesized from induced pluripotent stem cells

• Published in: Scientific reports Vol. 11; no. 1; pp. 14167 - 11
• Main Authors: Sato, Mai, Inohaya, Asako, Yasuda, Eriko, Mogami, Haruta, Chigusa, Yoshitsugu, Kawasaki, Kaoru, Kawamura, Yosuke, Ueda, Yusuke, Takai, Hiroshi, Mandai, Masaki, Kondoh, Eiji
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.07.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/136/2444; 631/532; Achievement tests; Animal models; Animals; Antigens; Biomarkers - metabolism; Bone Morphogenetic Protein 4 - pharmacology; Cell Differentiation - drug effects; Cell Line; Cell Lineage - drug effects; Cytokeratin; Diabetes mellitus; Female; Fetuses; Humanities and Social Sciences; Humans; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - drug effects; Liver diseases; Mice; Mice, Inbred NOD; Mice, SCID; multidisciplinary; Placenta; Placenta - cytology; Placenta - drug effects; Placenta - transplantation; Pluripotency; Pre-eclampsia; Preeclampsia; Pregnancy; Proteins; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Trophoblasts; Trophoblasts - cytology; Trophoblasts - drug effects; Trophoblasts - metabolism; Uterus; Uterus - physiology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-93766-9

Placental dysfunction is related to the pathogenesis of preeclampsia and fetal growth restriction, but there is no effective treatment for it. Recently, various functional three-dimensional organs have been generated from human induced-pluripotent cells (iPSCs), and the transplantation of these iPSCs-derived organs has alleviated liver failure or diabetes mellitus in mouse models. Here we successfully generated a three-dimensional placental organ bud from human iPSCs. The iPSCs differentiated into various lineages of trophoblasts such as cytotrophoblast-like, syncytiotrophoblast-like, and extravillous trophoblast-like cells, forming organized layers in the bud. Placental buds were transplanted to the murine uterus, where 22% of the buds were successfully engrafted. These iPSC-derived placental organ buds could serve as a new model for the study of placental function and pathology.