Research Overview

The value of induced pluripotent stem (iPS) cells in medicine lies in two major applications: (1) generating functional cells by recapitulating the developmental processes of target organs in vitro for use as transplantation materials, and (2) modeling disease mechanisms (pathology) to facilitate drug discovery. However, when multiple cell types are involved in a disease, it is extremely difficult to faithfully reproduce the pathology using iPS cells alone. Consequently, animal models such as mice remain indispensable for pathological analysis.

For example, the pathology of cancer is known to involve not only epithelial cells―the origin of tumor development―but also various other cell types, including surrounding stromal cells, vascular cells, and immune cells. Similarly, age-related decline in organ function involves not only the functional deterioration of the parenchymal cells themselves, which execute organ function, but also a state of chronic inflammation driven by the infiltration of immune cells.

Therefore, iPS cell-based approaches alone are not sufficient to unravel the pathology of cancer and aging.

Focusing on organs of endodermal origin such as the pancreas, our research strategy extends beyond maximizing the potential of iPS cells as described above; we simultaneously advance non-iPS cell-based research targeting organ regeneration, aging, and cancer. This dual approach is grounded in the commonalities observed between organ development―recapitulated during functional cell differentiation from iPS cells―and cellular behaviors during regeneration, aging, and cancer, such as robust cell proliferation and migration. (It should be noted, however, that the directionality of these processes differs: while organ development achieves functionality through concurrent cell differentiation and tissue architecture formation, cancer leads to the loss of organ function as a result of cell dedifferentiation and tissue destruction.) By adopting this perspective, we aim to maximize the synergies of conducting parallel research into organ development, regeneration, aging, and cancer.