The team is working on generating alveolar organoids from isolated mouse alveolar stem cells, as well as tracheal mesenchymal organoids from ES and iPS cells. Using alveolar organoids, they are carrying out research on stemness and heterogeneity of tissue stem cells, as well as research of disease models. With tracheal mesenchyme organoids, they are developing 3D culture methods for inducing cartilage tissue structures and aiming to understand mechanisms of tracheal cartilage patterning.

This team is studying self-organization mechanisms during nephron formation by quantitatively analyzing organ deformation and individual cell dynamics based on 4D imaging data of kidney organoid formation from human iPS cells and of mouse embryonic kidney development. In particular, we aim to provide clues for realizing organoid maturation by clarifying how the dynamics during the formation of organoid whose shape/size is immature differs from that during normal development. This study is performed in collaboration with Takasato Team.

The team aims to elucidate the tissue geometry-dependent maintenance of stem cell niches using intestinal organoids as a model. To investigate the effect of tissue morphological changes on niche maintenance, they will control the geometrical features of the extracellular matrix by micropatterning technique. Furthermore, they will uncover the molecular and mechanical mechanisms underlying the self-assembly of stem cells. This research has the potential to reveal the mechanism of stem cell niche maintenance that universally exists in various tissues beyond intestinal epithelium.

The team is aiming to generate a whole lower urinary tract, including the kidney and bladder, using human iPS cells. To do so, they are working to elucidate the mechanism regulating mesodermal cell differentiation and the patterning of endoderm-derived intestinal tube formation, and develop approaches to control these mechanisms. They are examining tissue vascularization mechanisms and applying their knowledge to develop technology for maintaining culture of 3D organs. They also aim to use kidney organoids to mimic and measure physiological renal functions in vitro.

This team applies microdevice technologies for organoid studies. Currently, the organoid culture needs to have a perfusion system or to have a technology to control its morphology into 3D arbitrary shape. The team will try to develop a technology to achieve these functions using various organoids handled by other members and study how the organoid can be cultured or matured using the technology.

The team is targeting on developing 3D culture platform enabling initial cell cluster shape control and dynamic control of morphogen gradient surround cells. By employing cubic culture device as well as microfabrication technique, they will array cells into arbitrary 3D shape in a hydrogel. Subsequently, morphogen gradient will be controlled by integrating the cube device into the microfluidic chip, so that spatial-temporal information required to the body axis formation will be added to the cells. The team collaborates with Morimoto team to investigate the pattern formation of the tracheal mesenchyme organoid by employing the developed platform.

The team is aiming to generate a whole lower urinary tract, including the kidney and bladder, using human iPS cells. To do so, they are working to elucidate the mechanism regulating mesodermal cell differentiation and the patterning of endoderm-derived intestinal tube formation, and develop approaches to control these mechanisms. They are examining tissue vascularization mechanisms and applying their knowledge to develop technology for maintaining culture of 3D organs. They also aim to use kidney organoids to mimic and measure physiological renal functions in vitro.

The team is aiming to develop an on-chip assay method to co-culture human iPSC-derived organoids and vasculature, based on a technology to create vascular network in a microfluidic device. It recapitulates an in vivo transplantation of organoids in vitro, which enables us to study tissue vascularization mechanisms on a chip. Furthermore, the team aims to mature organoids by long-term culture with perfusion through vasculature, and to apply the assay method to drug screening.

The team is working on generating alveolar organoids from isolated mouse alveolar stem cells, as well as tracheal mesenchymal organoids from ES and iPS cells. Using alveolar organoids, they are carrying out research on stemness and heterogeneity of tissue stem cells, as well as research of disease models. With tracheal mesenchyme organoids, they are developing 3D culture methods for inducing cartilage tissue structures and aiming to understand mechanisms of tracheal cartilage patterning.

The team is developing transplantation therapy using human iPS-derived retinal tissues (retinal pigment epithelium and photoreceptors) and gene therapy for the treatment of retinal degeneration diseases. To do so, they are improving the quality and culture methods of iPS cells and retinal organoids. Additionally, in order to constantly supply high-quality cells, which are currently produced by a handful of experienced researchers, a new technology is now being developed by combining the general-purpose humanoid robot, “Maholo”, and AI.

Our team establishes human iPS cells derived from patients with intractable diseases and generates genetically-engineered human iPS cells with genome editing technology in response to requests from the collaborative organoid project teams. Furthermore, the team will generate various organoids using disease-specific iPS cell lines deposited in the cell bank of the RIKEN BRC to contribute to research on intractable diseases and drug discovery and will develop cell culture technologies related to the organoid projects.

The team is developing transplantation therapy using human iPS-derived retinal tissues (retinal pigment epithelium and photoreceptors) and gene therapy for the treatment of retinal degeneration diseases. To do so, they are improving the quality and culture methods of iPS cells and retinal organoids. Additionally, in order to constantly supply high-quality cells, which are currently produced by a handful of experienced researchers, a new technology is now being developed by combining the general-purpose humanoid robot, “Maholo”, and AI.