Dept. of Cell Growth and Differentiation
Kazuo Takayama (Junior Associate Professor)
Kazuo Takayama Ph.D.
Human iPS cell-derived differentiated cells and organoids have promising prospects for application to drug discovery. Previous research has shown that they can contribute to drug discovery in areas from clarifying disease mechanisms to exploring drug candidates. Our laboratory is using human iPS cell-derived differentiated cells and organoids to research coronavirus disease 19 (COVID-19) and other infectious diseases. We are also applying organ-on-a-chip technologies to achieve physiologically relevant functions in human iPS cell-derived differentiated cells and organoids and to facilitate their use in drug discovery.
(1) Infectious disease research using human iPS cells
With infectious diseases such as COVID-19 infection having become a global issue in recent times, research using human iPS cell-derived differentiated cells and organoids is seen as a potential tool for elucidating the pathologies involved and advancing relevant drug discovery. Human iPS cell-derived differentiated cells and organoids can be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other pathogens to find out whether certain cells are susceptible to infection and how they respond to it. Additionally, these cells and organoids can be used to evaluate the efficacy of drug candidate compounds and predict their toxicity profile, potentially providing study data highly predictive of clinical response. Our research laboratory focuses specifically on organoids of the airway, liver, and colon to illuminate the pathological mechanism of infectious disease in these organs and to support drug discovery research. We also use CiRA's human iPS cell bank to reproduce individual differences in infectious disease symptoms and investigate their cause.
(2) Organ-on-a-chip technology to generate highly functioning human iPS cell-derived somatic cells
Organ-on-a-chip technology is a technique that simulates the in vivo dynamic cellular environment by applying mechanical stress to reproduce organ functions in vitro. Utilizing organ-on-a-chip technology makes possible the partial in vitro dynamic environment that occurs within the human body, such as blood and air flows, expansion and contraction, and peristaltic motion. It is expected that the organ chip technology will enable human iPS cell-derived differentiated cells and organoids to acquire a more organ-like appearance and reproduce some of the organ functions seen in vivo. We are working on the development of lung, intestinal, and liver chips and their application to drug discovery. We are also using these chips to research infectious diseases.
1) Exocyst complex component 2 is a potential host factor for SARS-CoV-2 infection
Yi R, et al., iScience. 2022 Nov 18;25(11):105427.
2) SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression
Hashimoto R, et al., Sci Adv. 2022 Sep 23;8(38):eabo6783.
3) Cell response analysis in SARS-CoV-2 infected bronchial organoids
Sano E, et al., Commun Biol. 2022 May 30;5(1):516.