(1) Viral infectious disease research using human iPS cells and organoids
With viral infectious diseases such as COVID-19 infection becoming a global issue in recent years, research using human iPS cells and organoids is commonly seen as a potential tool for elucidating the pathologies involved and advancing relevant drug discovery. Human iPS cells and organoids can be used to determine whether certain cells are susceptible to infection with SARS-CoV-2 or other pathogens and how they respond to it. Additionally, these cells and organoids are applicable for evaluating the efficacy of drug candidate compounds and predicting their toxicity profiles, potentially providing preclinical data highly predictive of clinical responses. In our laboratory, we continue to analyze host factors related to SARS-CoV-2 using human iPS cells and examine for individual differences in infections. In addition, we are also characterizing SARS-CoV-2 and RSV and performing drug discovery research using respiratory organoids.

(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 not only recreates the three-dimensional cellular environment with multiple types of cells consisting of a specific organ inside a microfluidic device but also includes mechanical stimulations to reproduce organ functions in vitro. Utilizing organ-on-a-chip technology that partially recapitulates in vitro the dynamic environment within the human body, such as blood and air flows, expansion and contraction, and peristaltic motion. Culturing human iPS cells and organoids in microfluidic devices achieves more organ-like structures and reproduces some organ functions seen in vivo. We are developing respiratory-, liver-, and intestinal-on-a-chips and applying them to research on viral infectious diseases. For example, by using a respiratory-on-a-chip to analyze the SARS-CoV-2 variants, it is possible to evaluate the ability of each variant to disrupt the respiratory epithelial-endothelial barrier.

1) Virological characterization of the 2022 outbreak-causing monkeypox virus using human keratinocytes and colon organoids
Watanabe Y, et al., J Med Virol. 2023 Jun;95(6):e28827.

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) Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips
Deguchi S, et al., PNAS Nexus. 2023 Mar 7;2(3):pgad029.