INTRODUCTION‘‘Organoid technology’’

INTRODUCTION‘‘Organoid technology’’ is a recently evolving approach for the treatment of intractable diseases as well as human models of development and disease (Huch and Koo, 2015; Lancaster and Knoblich, 2014; Sasai, 2013). Based on a self-condensation principle, we recently succeeded in building an additional complexity into organoids by developing multicellular organ buds (such as liver bud, pancreatic bud, and kidney bud) with therapeutic potential against various mouse disease models (Takebe et al., 2013, 2014, 2015). Nevertheless, broader applica- tions of an organoid-based approach are subject to scalability and reproducibility challenges, and one must produce an organoid large and stable enough for transplantation and drug testing in humans (Ding and Cowan, 2013). To facilitate the future therapeutic application of organ-bud-based approaches, we aimed to establish a comprehensive, scalable, and reproducible method for generating vascularized human liver buds (LBs) entirely from feeder-free human induced pluripotent stem cells (iPSCs) and validate their functional capacity for transplant application.