The Takebe Lab enjoys developing new technology and implementing fresh outlooks on discoveries that may be ignored, under-appreciated and overlooked by the traditional scientific community. The Takebe Lab takes a creative lead for the exploitation and dissemination of unpredictable, extraordinary and crazy paradigm by integrating discovery and technology, eventually revolutionizing science, and medico-health-care paradigm. The Takebe Lab is also lending its support to commercial execution to move forward.

The self-organizing tissue-based approach coupled with induced pluripotent stem cell (iPSC) technology has just begun as a promising field for designing a miniature organ, aka an organoid, in culture and is expected to achieve valuable outcomes in ‘(re-) generative medicine’ and ‘drug development’. However, how the complex but stereotyped tissue shapes self-organize still remains largely unknown. To understand such complex self-organizing mechanisms, Dr Takebe’s lab proposes to take a ‘reverse reductionism approach’ for a holistic mechanistic understanding of the dynamic nature of a self-developing system. We also seek to translate knowledge of living systems into a revolutionary technology platform towards practical biomedical use in clinics.

Organoids are multicellular structures that can be derived from adult organs or pluripotent stem cells. Early versions of organoids range from simple epithelial structures to complex, disorganized tissues with large cellular diversity. The current challenge is to engineer cellular complexity into organoids in a controlled manner that results in organized assembly and acquisition of tissue function. These efforts have relied on studies of organ assembly during embryonic development and have resulted in development of organoids with multilayer tissue complexity and higher order functions. To advance the field forward, Takebe Lab would like to achieve three interactive and complementary goals:

1. The deductive development of a complex human organoid model

2. The multidisciplinary dissection of self-driven mechanisms of organogenesis

3. The technology prototyping towards biomedical applications

Our early efforts are being made on liver organoid (liver bud or miniature liver) systems using human iPSC. For example, we have demonstrated successful integration of endothelial cells (Nature, 2013), mesenchymal cells (Cell Stem Cell, 2015) and macrophages (Cell Metab, 2019) into human liver organoids, allowing for the study of drug testing and transplant applications. More recently, we showed the inter-coordinated specification and invagination of the human hepato-biliary-pancreatic system from human pluripotent stem cells, thereby, connecting multi-organ systems in a dish (Nature, 2019). Thus we are tackling the questions how the next generation of organoids can be designed by utilizing an engineering-based narrative design, and what promise and impact will be brought towards future biomedical applications (Science, 2019). Our interested expertise includes cell biology, mathematics, bioinformatics, morphogenesis, genomics, bioengineering, chemistry or biomechanics. In a longer term, we seek to realize “organoid medicine” applications through human implementation of extracorporeal device, precision medicine, drug discovery and organ replacement therapy. We are accelerating such biomedical applications of organoids by collaborating with international and diverse industry collaborators, such as the Cincinnati Children’s Hospital and the Takeda-CiRA program.