Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells

Posted on Posted in AMRC Research

Date: 06 Dec 2017

 

Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive “reverse” screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass producing homogeneous and miniaturized liver buds on a clinically relevant large scale (>108). Vascularized and functional liver tissues generated entirely from iPSCs significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacturing platform for multicellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations.

 

Link to full article

 

For inquiries regarding this press release

Takanori TAKEBE

E-mail: ttakebe@yokohama-cu.ac.jp   Phone: +81 45 787 2672

 

Hideki TANIGUCHI

E-mail: rtanigu@yokohama-cu.ac.jp   Phone: +81 45 787 2672

 

Department of Regenerative Medicine,
Yokohama City University School of Medicine

Fukuura 3-9, Kanazawa-ku, Yokohama, 236-0004 JAPAN