Conference Chairman Welcome and Opening Remarks and Introduction to the Cell Therapy Space, circa 2018
Norio Nakatsuji, Chief Advisor, Stem Cell & Device Laboratory, Inc. (SCAD); Professor Emeritus, Kyoto University, Japan

Conference Chairman Welcome and Opening Remarks and State of Regenerative Medicine Industry
Yuzo Toda, President, FIRM (Forum for Innovative Regenerative Medicine, Japan), Japan

Retinal Cell Therapy Using iPS Cells
Masayo Takahashi, Professor, RIKEN Center for Biosystems Dynamics Research, Japan

The first in man application of iPS-derived cells started in September 2014, targeted age-related macular degeneration (AMD).  AMD is caused by the senescence of retinal pigment epithelium (RPE), so that we aimed to replace damaged RPE with normal, young RPE made from iPS cells. We judged the outcome 1 year after the surgery. Primary endpoint was the safety, mainly the tumor formation and immune rejection. The grafted RPE cell sheet was not rejected nor made tumor after two years. The patient’s visual acuity stabilized after the surgery whereas it deteriorated before surgery in spite of 13 times injection of anti-VEGF in the eye. Since autologous transplantation is time consuming and expensive, it is necessary to prepare allogeneic transplantation to establish a standard treatment. RPE cells are suitable for allogeneic transplantation because they suppress the activation of the T-cell. From in vitro and in vivo study, it is possible that the rejection is considerably suppressed by using the iPS cell with matched HLA. Our new protocol has accepted by ministry in Feb 2017. We are planning transplantation using allogeneic iPS-RPE cell suspension & sheet, and also autologous iPS-RPE. For the cell suspension transplantation we will not combine CNV removal and apply to milder cases than sheet transplantation. In Japan, pharmaceutical law has been changed and a new chapter for regenerative medicine was created for clinical trial. Also the separate law for safety of regenerative medicine for clinical research (study) was enforced in 2015. These laws made the suitable condition for the brand new field of regenerative medicine. We are making regenerative medicine in co-operation with ministry & academia.

Regenerative Medicine in Astellas
Yoshitsugu Shitaka, President, Astellas Institute for Regenerative Medicine, Japan

Astellas Institute for Regenerative Medicine (AIRM) was established in May 2016 following Astellas’ acquisition of Ocata Therapeutics. AIRM is an indirect, wholly owned subsidiary of Astellas and serves as Astellas’ global hub for RM and cell therapy in ophthalmology and other therapeutic areas that have few or no available treatment options.  The outline of Astellas RM will be reviewed in this presentation.

Translating Stem Cell Research: Challenges At Front Line
Hiromitsu Nakauchi, Prof of Genetics, Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine Project Professor, The Institute of Medical Science, Division of Stem Cell Therapy, Distinguished Professor Unit, The University of Tokyo, United States of America

The recent development of induced pluripotent stem cell (iPSC) technology opened the way to regenerative medicine using a patient’s own PSC-derived cells.  In this presentation, I describe some of our iPSC technology-based projects aiming at clinical use.

Cell Fiber Technology For 3D Tissue-on-a-Chip Application
Shoji Takeuchi, Professor, Center For International Research on Integrative Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, Japan

The talk describes a 3D cell culture method using core-shell hydrogel microfibers (cell fibers). The core is filled with cells and ECM proteins, and the shell is composed of calcium alginate. Since the core diameter is about 100 microns, oxygen and nutrients can be diffused into the central area of the 3D tissue; therefore this culture system allows us to culture the tissue for a long period without central necrosis. Using this culture system, fiber-based tissues such as blood vessels, nerves, and muscles can be formed with in the core. Here, I will discuss the application of the cell fiber technology for various tissue-on-a-chip studies including cardiac tissue, neuro-muscular junctions, and vascularized skin etc.

Intelligent Image-Activated Cell Sorting
Keisuke Goda, Professor of Chemistry, University of Tokyo and Adjunct Professor, Wuhan University, Japan

A fundamental challenge of biology is to understand the vast heterogeneity of cells, particularly how cellular composition, structure, and morphology are linked to cellular physiology. Unfortunately, conventional technologies such as fluorescence-activated cell sorting are limited in uncovering these relations. In this talk, I introduce our machine intelligence technology known as “Intelligent Image-Activated Cell Sorting” [Cell 175, 1 (2018)] that builds on a radically different architecture that realizes real-time image-based intelligent cell sorting at an unprecedented rate. This technology integrates high-throughput cell microscopy, focusing, and sorting on a hybrid software-hardware data-management infrastructure, enabling real-time automated operation for data acquisition, data processing, decision-making, and actuation. I show the application of the technology to real-time image-activated sorting of microalgal and blood cells based on intracellular protein localization and cell-cell interaction from large heterogeneous populations for studying photosynthesis and atherothrombosis, respectively. The technology is highly versatile and expected to enable machine-based scientific discovery in biological, pharmaceutical, and medical sciences including cell therapy.

Questions to Ask when Designing 3D Cell Culture Model Systems
Terry Riss, Senior Product Manager, Cell Health, Promega Corporation, United States of America

There continues to be a rapid expansion in the use of 3D cell culture model systems because they more closely represent the in vivo situation compared to culturing cells as a monolayer attached to plastic. There are many approaches classified as 3D culture models ranging from individual scaffold-free spheroids to human-on-a-chip and researchers soon become aware the models have vastly different requirements and there is no “one size fits all” approach. Selecting a 3D culture model that is “fit for purpose” involves several decisions and often results in a compromise between sample throughput and culture model complexity or cost. We will describe an overview of factors to consider when designing or selecting an appropriate 3D culture model addressing: sample size, scaffolds, culture medium, choice of assay methods, and reproducibility. Attendees should acquire an increased awareness of the range of available approaches and be able to use the information to design an appropriate 3D culture model.

Chemically Induced Liver Progenitors as a Source for Liver Regeneration and Organ Reconstruction
Takahiro Ochiya, Professor, Department of Molecular and Cellular Medicine, Tokyo Medical University, Japan

We currently report that a cocktail of small molecules can convert rat and mouse MHs in vitro into proliferative bipotent cells, which we term chemically induced liver progenitors (CLiPs) (Katsuda et al., Cell Stem Cell, 2017). CLiPs can differentiate into both mature hepatocytes and biliary epithelial cells that can form functional ductal structures. CLiPs in long-term culture did not lose their proliferative capacity or their hepatic differentiation ability, and rat CLiPs were shown to extensively repopulate chronically injured liver tissue. Our current progress on generation of human CLiPs from human mature hepatocytes and the therapeutic potency for liver diseases as well as potency of drug metabolism and towards organ reconstruction will be mentioned.

iPSC-based Cell Therapy and Modeling of Neural Disorders
Hideyuki Okano, Professor, Department of Physiology, Keio University School of Medicine, Japan

What makes the investigation of human psychiatric/psychiatric disorders so difficult? This could be attributed to the following reasons 1) Diseases model mice do not always recapitulate the pathophysiology of human diseases, 2) It is extremely difficult to investigate what is taking place in vivo at the onset of the disease due to the low accessibility to the pathological foci in the brain, and 3) The responsible neuronal circuits for the phenotype are not identified. In order to overcome these difficulties, we took advantage of iPS cell technologies and transgenic non-human primates for modeling human psychiatric/psychiatric disorders. So far, we have established iPS cells from the patients of about 40 human psychiatric/psychiatric disorders and characterized their pathophysiology, including Alzheimer disease, Parkinson disease, ALS, Rett syndrome (and Pelizaues-Merzbacher disease. I will talk about how we are developing new drugs for ALS using iPS cells technology. Furthermore, for faithfully modeling the human psychiatric/psychiatric disorders in vivo, we developed transgenic non-human primates (common marmosets) with germline transmission. In the present talk, we also wish to mention our recent data of generation of common marmoset transgenic models of neurodegenrerative diseases, including Parkinson disease. Furthermore, we have done the deep sequencing of marmoset whole genome with NGS could generate knock-out technologies of common marmoset using genome editing technologies for the generation of transgenic marmoset model of autism and psychiatric disorders.

How to Regulate Unproven Cellular Therapies, Beyond “Right to Try”
Kunihiko Suzuki, Vice Chairman & Member of the Board, Medinet Co. Ltd., Vice Chair, Forum for Innovative Regenerative Medicine (FIRM), Japan

There are some movement recently in regulation for so-called “unproven cellular therapies” (UCT)/“unregulated market product”, which private hospitals/clinics may provide medical care/medical treatment to patients. According to the report (Cell Stem Cell 19, August 4, 2016 Elvsevier Inc.), there are 570 clinics which offer stem cell interventions to the public without any market authorization as a product from FDA.  In addition, in November last year, FDA published 4 Guidances for HCTPs, which seem to put on target towards UCTs and gave warning letters to the clinics in California and also Miami, FL.  However, at the same time, “Right to try” bills are under lots of discussions among the various parties. In general, there has been no specific regulation to control the activities of medical care/medical treatment by medical doctors/dental doctors before Japan introduced “The Act on the Safety of Regenerative Medicine” (ASRM).  With the new regulation in Japan, we can reach to the statistics of clinics/hospitals which involve care/treatment with non market-authorized products by MHLW/PMDA and/or the details of such medical care/medical treatment. It is worthwhile for everyone in this space to learn benefit/outcome/limitation on ASRM to bring cutting-edge medical technologies with safe and efficacious manner to the patients. Hope Japanese regulatory framework will be the pilot model for the regulations of other countries in future.

Commercialization of Cell Therapies – Laboratory to Bedside
Michael Bennett, Director of Business Development, Cell and Gene Therapy Catapult, United Kingdom

There are many teams of scientists working diligently in the broad field of regenerative medicine.  The goal of much of this work is to create new medicines that have the potential to cure debilitating diseases that conventional small molecule medicines cannot.  In my presentation I will discuss some of the challenges facing us all within regenerative medicine and some of the solutions that the cell and gene therapy catapult has seen implemented around the world to assist the commercialisation of promising laboratory science through pre-clinical testing, clinical trial and to the patient bedside.