Abstract: Cell therapy represents a significant development in modern medicine, providing new avenues for treating various diseases. Among these, the application of induced pluripotent stem (iPS) cells in ocular diseases has been a notable area of research. Since 2014, the Kobe City Eye Hospital's team has been using iPS cells to treat age-related macular degeneration (AMD). Studies in 2014 [1] and 2018 [2] confirmed the safety of these cells, leading to planned transplants in 10 to 100 patients. However, large-scale cell manufacturing for numerous patients presents challenges, which can be overcome through automation using robots. To make this feasible for clinical use, it is essential to minimize costs, including money and time, and employing robots is necessary to achieve these cost reductions.
We selected the versatile humanoid robot Maholo Labdroid [3] as an AI/robotic system for retinal regenerative medicine research and demonstrated its utility. Firstly, we confirmed that basic cell culture operations, such as passaging and microscopic observation, could be successfully performed using HEK293A (Human embryonic kidney cell line) cells, which are relatively easy to handle [4]. Next, we tested more practical procedures using iPS cells, which require more careful handling. We implemented a process in the robot for differentiating iPS cells into retinal pigment epithelium (RPE) cells, including seeding, medium exchange, and passage. We demonstrated that with the appropriate parameters, the robot could produce differentiated cells of a quality comparable to those cultivated by experienced technicians [5]. Humanoid robots, which are capable of performing tasks similar to those of humans, have great potential, but their application in clinical research requires the establishment of a sterile environment. To address this issue, we combined a humanoid robot with an air-barrier booth (R-CPF: robotic cell processing facility) and examined the maintenance of cleanliness during the actual work process. The combination of a robot and air-barrier booth can achieve the sterile environment required for clinical research. Moreover, the cells manufactured using the robot maintained the sterile state necessary for clinical research [6].
Based on these results, in February 2022, the Kobe City Eye Hospital received approval from the regulatory authorities to use Maholo LabDroid for clinical research. Additionally, in December 2022, it was announced that cells cultured by the robot were transplanted into patients. Humanoid robots have finally reached the clinical treatment stage. In this session, we would like to discuss the background of these developments and explore how AI/robots shape the future of therapeutics.
[1] Mandai et al, NEJM, 2017 [2] Sugita et al, J Clin Med Res, 2020 [3] Yachie et al, Nat Biotechnol, 2017 [4] Ochiai and Motozawa et al, SLAS Technol, 2020 [5] Kanda and Tsuzuki et al, eLife, 2022 [6] Terada et al, SLAS Technol, 2023
