Organoids and Organ-on-a-Chip Asia 2023 Agenda

Title to be Confirmed.
Peter Ertl, Professor of Lab-on-a-Chip Systems, Vienna University of Technology, Austria

MPS Platforms with High Operability for Commercialization
Hiroshi Kimura, Professor, Micro/Nano Technology Center, Tokai University, Japan

Microphysiological systems (MPSs) have been widely studied as a novel method for estimating the effects and toxicities of drugs, providing an alternative to animal tests in drug discovery. In EU and USA, various types of MPS are commercially available by some companies, and more recently, their practical application has been well promoted. Although MPS has been actively researched in Japan, there has been almost no practical MPS to date. Japan Agency for Medical Research and Development (AMED) has conducted an MPS development project with the aim of commercializing domestically produced MPS since 2017. Our research group has developed two types of MPS, Fluid3D-X and Kinetic pump Integrated Microfluidic Plate, for commercialization in collaboration with Japanese manufacturing companies in the project. Our proposed MPSs are expected to facilitate high quality cell-based assays in drug discovery and biology due to their ease of use and high throughput. In this presentation, I present the overview of these MPS’s functions and examples of the drug evaluation studies using the MPSs.

Initiatives of AMED-MPS Projects for Industrial Implementation of MPS in Japan and Collaboration with Asia
Seiichi Ishida, Guest Researcher, National Institute of Health Sciences, Professor, Sojo University, Japan

AMED-MPS2 project started in 2022 and has been leading the initiative for the implementation of MPS originated in Japan to industries. Due to the unique nature of the culture environment of MPS, it has become clear that there are "points to consider" that differ from conventional culture methods in order to maintain healthy cell function,e.g. cell functionality, cell adhesion property, and medium perfusion conditions. Our efforts how to deal with such requirements for MPS industrial implementation will be introduced. Beyond these efforts will be the regulatory acceptance of the data obtained by MPS. Discussions what MPS should be as the test methods for regulatory usage based on the considerations will be presented, which are taking place in AMED MPS-RS (RS stands for “regulatory science”). MPS-RS has launched MPS Consortium for Industrial Implementation and Regulatory Acceptance, which gives the discussion table among four stakeholders, academia, supplier, end user, and regulator. The MPS Consortium are also collaborating with iMPSS, founded in this June, and its Asia-Pacific regional chapter. These activities will be presented.

Microphysiological Systems (MPS) With Perfusable Vascular Network for Pharmacological and Organogenesis Applications
Ryuji Yokokawa, Professor, Department of Micro Engineering, Kyoto University, Japan

Microfluidic devices have been used to answer scientific questions in many lifescience research fields. Microphysiological systems (MPS) mimics the functions of human biological organs and can be used to measure physiological functions that are difficult to measure on a culture dish. We have employed two approaches to create the interface between organ cells and vascular networks: a two-dimensional method in which organ cells and vascular endothelial cells are co-cultured on a porous membrane such as Transwell (2D-MPS), and a three-dimensional method in which the spontaneous patterning ability of vascular endothelial cells is utilized (3D-MPS). As an example of 2D-MPS, we developed a renal proximal tubule model and a glomerular filtration barrier model using iPSC-derived organoid cells, which enables us to evaluate reabsorption, filtration, and nephrotoxicity. For 3D-MPS, angiogenesis and/or vasculogenesis are utilized to anastomose a fibroblast spheroid and tumor spheroids to create tumor microenvironments to evaluate the efficacy of an anti-tumor drug under a flow condition. We also developed an on-chip vascular bed to co-culture with any kind of tissues that do not have enough angiogenic factors to induce angiogenesis. It was applied to kidney and brain organoids for evaluating the effect of vessels on their development. The vascular bed chip enabled to culture a kidney organoid at the air-liquid interface (ALI) that is required for nephrogenesis and to separately supply two media for the organoid and vascular bed. Proposed assay platforms will further contribute to realize pharmacological applications and to understand in vivo organogenesis. We keep exploring how micro/nano fabrications can deepen science at the interface between blood vessels and organs.

The NIH Microphyiological Systems Program: In Vitro 3D Models for Safety and Efficacy Studies
Danilo Tagle, Director, Office of Special Initiatives, National Center for Advancing Translational Sciences at the NIH (NCATS), United States of America

Approximately 30% of drugs have failed in human clinical trials due to adverse reactions despite promising pre-clinical studies, and another 60% fail due to lack of efficacy. A number of these failures can be attributed to poor predictability of human response from animal and 2D in vitro models currently being used in drug development. To address this challenges in drug development, the NIH Tissue Chips or Microphysiological Systems program is developing alternative innovative approaches for more predictive readouts of toxicity or efficacy of candidate drugs. Tissue chips are bioengineered 3D microfluidic platforms utilizing chip technology and human-derived cells and tissues that are intended to mimic tissue cytoarchitecture and functional units of human organs and systems. In addition to drug development, these microfabricated devices are useful for modeling human diseases, and for studies in precision medicine and environment exposures. Presentation will elaborate in the development and utility of microphysiologicals sytems and in the partnerships with various stakeholders for its implementation.