Dept. of Cell Growth and Differentiation
Kazuo Takayama (Junior Associate Professor)
Kazuo Takayama Ph.D.
Human iPS cells and their derivatives 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 cells and their derivatives to research coronavirus disease 19 (COVID-19) and other infectious diseases. We are also applying organ-on-a-chip technologies such as microfluidic devices and pumps to achieve physiologically relevant functions in human iPS cell-derived cells and to facilitate their use in drug discovery.
(1) Infectious disease research using human iPS cells and organoids
With the recent global spread of SARS-CoV-2, human iPS cells and their derivatives are being seen as a potential tool for clarifying pathologies and for drug discovery. By infecting iPS cell-derived somatic cells with SARS-CoV-2, we can find out whether certain cells are susceptible to infection and how they respond to it. These cells can also be used to evaluate the drug efficacy of candidate compounds and predict their toxicity profile. Among various somatic cells, we are focusing on airway epithelial cells, which are one of the initial infection cells of SARS-CoV-2. Therefore, we have generated airway organoids and used them for SARS-CoV-2 research. Using airway organoids, we aim to clarify the pathophysiology of COVID-19 and develop new therapeutic agents for COVID-19. Additionally, we are using CiRA's human iPS cell bank to reproduce individual differences in the symptoms of COVID-19 and discover 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 the 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. By using this technology with human iPS cell-derived somatic cells, it should be possible to generate more physiologically relevant conditions, allowing some of the organ functions to be reproduced as they exist in vivo. Our laboratory is working to develop lung-, liver-, and intestine-on-a-chips for pharmaceutical research. We are also using these chips to research infectious diseases.
1) Dual inhibition of TMPRSS2 and Cathepsin B prevents SARS-CoV-2 infection in iPS cells
Hashimoto R, et al., Mol Ther Nucleic Acids. 2021 Dec 3;26:1107-1114.
2) Cell response analysis in SARS-CoV-2 infected bronchial organoids
Eano E, et al., Commun Biol. 2022 May 30;5(1):516.
3) Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells
Eano E, et al., iScience. 2021 May 21;24(5):102428.