08:00 | Conference Registration, Materials Pick-Up, Morning Coffee and Pastries |
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Session Title: Conference Opening Session |
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08:30 |  | Conference Chair Chairman's Welcome, Introduction to the Conference and Technology Landscape of 3D-Culture
Terry Riss, Senior Product Manager, Cell Health, Promega Corporation, United States of America
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09:00 |  | Keynote Presentation Generating Human Liver Spheres From Pluripotent Stem Cells and Their Application
David Hay, Chair of Tissue Engineering, MRC Centre for Regenerative Medicine, University of Edinburgh, United Kingdom
Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, there are a shortage of donor organs. Therefore, developing renewable sources of human liver tissue is important for the clinic. Pluripotent stem cell-derived liver tissue represents a potential alternative to cadaver derived hepatocytes and whole organ transplant. At present, two-dimensional differentiation procedures deliver tissue that is hepatocyte like, but lacks certain functions and long-term stability. Efforts to overcome these limiting factors have focussed on building three-dimensional (3D) cellular aggregates. Although enabling for the field, their widespread application has been limited due to cost and overreliance on undefined biological components. Our studies focused on the development of self assembled 3D liver tissue under defined conditions. In vitro generated 3D tissues exhibited stable phenotype, providing an attractive resource for the clinic and long-term in vitro modelling studies. Our most recent tissue engineering advances will be discussed at the meeting. |
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09:30 |  | Keynote Presentation Vascularized Tumor Spheroids for Drug Screening on Injection Molded IMPACT Platform
Noo Li Jeon, Professor, Seoul National University, Korea South
The field of microfluidics-based three-dimensional (3D) cell culture systems is rapidly progressing from academic proof-of-concept studies to valid solutions to real-world problems. Polydimethylsiloxane (PDMS)-based microfluidics platforms have been widely adopted for tumor-on-a-chip systems. However, due to the inherent material limitations that make it difficult to scale-up production, PDMS has not been widely used in standardized commercial applications for preclinical screening testing. In this presentation, injection-molded tumor spheroid chip made of polystyrene (PS) in a standardized 96-well plate format with a user-friendly design. Spontaneous liquid patterning is achievable with high repeatability. To demonstrate the feasibility of the device, we fabricated array of vascularized tumor spheroids and developed a 3D tumor angiogenesis model for drug screening. This model is easy- and ready-to-use, and suitable for mass-production systems, with the ability to deliver robust and reproducible results. |
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10:00 | Morning Coffee Break and Networking in the Exhibit Hall |
10:45 |  | Keynote Presentation Utilizing Multi-Organ Human on a Chip Systems to Predict in vivo Outcomes For Efficacy and Toxicity
James Hickman, Professor, Nanoscience Technology, Chemistry, Biomolecular Science and Electrical Engineering, University of Central Florida; Chief Scientist, Hesperos, United States of America
The utilization of multi-organ human-on-a-chip or body-on-a-chip systems for toxicology and efficacy, that ultimately should lead to personalized medicine applications, is a topic that has received much attention recently for drug discovery and subsequent regulatory approval. Hesperos has been constructing these systems with up to 6 organs and have demonstrated long-term (>28 days) evaluation of drugs and compounds, that have shown similar response to results seen from clinical data or reports in the literature. Application of these systems for ALS, Alzheimer’s, rare diseases, diabetes and cardiac and skeletal muscle mechanistic toxicity will be reviewed. The development of an in vitro PDPK modeling that predicts in vivo results will also be presented. The system utilizes a pumpless platform with a serum free recirculating medium. This methodology integrates microsystems fabrication technology and surface modifications with protein and cellular components, for initiating and maintaining self-assembly and growth into biologically, mechanically and electronically interactive functional multi-component systems. Hesperos has received Phase II and Phase IIB SBIR grants from NCATS to apply Advanced Manufacturing Technologies and automation to these systems in collaboration with NIST in addition to support form pharmaceutical and cosmetic companies. This talk will also give results of six workshops held at NIH to explore what is needed for validation and qualification of these new systems. |
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11:15 |  Complex 3D In-Vitro Liver-Disease Models For Fast, Automation-Compatible and Translational Drug Discovery
Jan Lichtenberg, CEO and Co-Founder, InSphero AG
Scaffold-free 3D microtissues have evolved into the most widely used technology for highly predictive and most scalable cell-based assays in drug safety and discovery. While they provide a faithful in-vitro approximation of the in-vivo tissue microenvironment, they were not amenable for modeling microphysiological features up to now. Focusing on advantages and challenges in daily industry use, we’ll describe two case studies illustrating how a 3D microtissue can be used as a predictive surrogate for drug discovery. One study investigates a complex co-culture system recapitulating the hallmarks of nonalcoholic steatohepatitis (NASH) in a screening-compatible format. Consisting of primary human hepatocytes, NPCs and stellate cells, these 3D microtissues can be elastically driven into and out of specific disease states. As second application, we will describe the use of reconstituted, 3D primary human pancreatic islets for discovery of anti-diabetic drugs. Finally, we present a new multi-organ-on-a-chip system featuring microfluidic channels and chambers that were specifically engineered for culturing 3D microtissues and organoids under physiological flow conditions. The platform complies with the SBS plate standard and is made of polystyrene to prevent unwanted compound absorption. It allows for an automated and on-demand interconnection of up to 10 microtissues per channel in a highly flexible fashion. Enabling an automated removal and re-insertion of 3D microtissues from and into the device, this platform finally ads deep endpoints such as next-gen sequencing, lipidomics, FACS to the analytical toolbox for organ-on-a-chip applications. Summarizing, we will focus on the major challenges encountered when implementing human, primary cell based 3D and organ-chip assays – and our suggestions on how to address them in an industry-wide effort.
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11:45 |  | Keynote Presentation Merging Organ-on-a-Chip with Organoids: The Best of Two Worlds?
Paul Vulto, Managing Director, MIMETAS, Netherlands
Organ-on-a-Chip and organoids are two fields of development that are rapidly redefining cell culture biology in the 21st century. Organ-on-a-Chip technology has demonstrated how microengineering technology can add aspects such as perfusion flow, patterning of tissues, precise control over gradients and application of mechanical strain to tissue culture. Organoid protocols have been carefully optimized to maintain the stem cell niche in developing and adult tissues, while at the same time permitting cell proliferation and differentiation.
In this lecture, I will show latest progress at MIMETAS integrating organoid protocols and Organ-on-a-Chip technology. I will show a range of tissue models comprising complex co-cultures, in a perfused system using state of the art stem cell and organoid protocols. Following this presentation, it will become clear that the two fields are merging together to aid cell culture of the 21st century. |
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12:15 | Networking Lunch in the Exhibit Hall and Poster Viewing |
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Session Title: Organoids and 3D-Culture - Technologies and Applications |
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Emerging Themes in Organoids and Organs-on-Chips: An Introduction |
| Session Chair: Paul Vulto, Managing Director, MIMETAS, Netherlands |
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13:30 | Phenotypic Screening in 3D Culture Including ECM: Advantages and Challenges
Nathalie Maubon, CEO/CSO, HCS Pharma, France
Grégory Maubon, Digital Coordinator, HCS Pharma, France
Cellular assays in 3D culture have shown many advantages to better mimic the in vivo situation. 3D technologies for phenotypic screening have become simpler and more accessible, such as the use of Ultra Low Attachment (ULA) plates. However, we can now go even further using 3D technologies which allow us to reproduce the micro-environment of healthy or pathological organs of interest. During this talk, we will show how the cellular microenvironment impacts the proliferation and/or differentiation of cells. A few examples from the fields of oncology, CNS and metabolic disease will be presented. High-Content Screening (HCS) devices, such as our ImageXpress® Micro Confocal system, are now fast enough and sensitive enough to allow image acquisition in 3D cellular models. Nevertheless, to go further, perceptions and processes need to be changed. We will discuss cutting-edge new technologies, including virtual and augmented realities, deep learning and machine learning, and explain how these new technologies can be of benefit to phenotypic screening. |
14:00 | 3D Hydrogel as Clinically-Relevant Neuroblastoma Model Where to Test Novel Antibody-Mediated Therapies
Silvia Scaglione, Professor, National Council of Research (CNR), Genoa (Italy) and Head of Laboratory of Tissue Engineering, Italy
A 3D cell-laden alginate hydrogels was designed as in vitro neuroblastoma model. The system revealed a clinical-relevant constitutive and IFN-gamma inducible NB immunophenotype suggesting its potential as future platform for set up and validate immune based therapeutic approaches. |
14:30 | BrainSpheres to Study Developmental Neurotoxicity
David Pamies, Researcher, University of Lausanne, Switzerland
Developmental neurotoxicity is of high concern due to different reasons: 1) no routine testing for DNT is carried out in the U.S., in the EU, or elsewhere, as DNT testing is not required by law unless triggered by neurotoxic or endocrine effects in adult rodents, 2) DNT guidelines are expensive and time-consuming, 3) human brain complexity may not be completely tested by animal testing, and 4) brain defects can be difficult to detect. Experts in the field have suggested an in vitro testing battery to cover brain development key events (such as neural stem cell proliferation and differentiation, migration, neurite outgrowth, synaptogenesis, network formation, myelination, and apoptosis). Also, the use of more human-relevant models, using 3D organotypic iPSC derived systems, have been suggested as an alternative to classical in vitro models. Here we present a 3D brain human-derived iPSC model to study developmental neurotoxicity and different applications of the model. |
15:00 | Afternoon Coffee Break and Networking in the Exhibit Hall and Poster Viewing |
15:30 |  Magnetic 3D Bioprinting, from Spheroids to Fingerprinting Cells in 3D Using a 2D Workflow
Glauco Souza, Director of Global Business Development and Innovation, 3D Cell Culture at Greiner Bio-One; Adjunct Assistant Professor, Greiner Bio-One and University of Texas Health Science Center at Houston
The growing push for 3D cell culture models is limited by technical challenges in handling, processing, and scalability to high-throughput applications. To meet these challenges, we use our platform, magnetic 3D bioprinting, in which cells are individually magnetized and assembled with magnetic forces. In magnetizing cells, not only do we make routine cell culture and experiments feasible and scalable, but we also gain fine spatial control in the formation of spheroids and more complex structures. This presentation will focus on recent developments using this platform, particularly in cancer biology and immunology. Specifically, we will present a method for phenotypic profiling of cell types within spheroids using real-time high-throughput imaging. This label-free method allows for multiplexing with other assay endpoints for high-content screening. Overall, we use magnetic 3D bioprinting to create functionally and structurally representative spheroids for high-throughput screening.
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16:00 | High Content Screening of Organoid Cultures to Visualize and Quantify Intestinal Toxicity
Bram Herpers, COO, OcellO B V, Netherlands
Establishing organoids from human material enables development of 3D cell culture models for the intestinal epithelium to investigate physiological and toxicological mechanisms. At OcellO we combine a high throughput 3D human intestinal organoid culture platform with high content phenotype-based analysis to visualize and quantify the effects of compounds and treatment conditions on the epithelial integrity, injury and inflammation in a diverse (healthy and diseased) patient-derived organoid population. |
16:30 | 3D Microtumor-based Combinatorial Drug Discovery
Jens Kelm, CEO and Co-Founder, PreComb Therapeutics AG, Switzerland
3D tissue culture technologies for drug discovery are becoming of age. However, new 3D technologies and models are primarily used to exchange existing models to improve individual aspects in the developmental process. However, 3D models do not only reflect tissue and organ disease biology better than 2D models they allow to create novel assays to build completely new drug development processes. To take full advantage of 3D we present a 3D-based discovery processes to develop novel drug combinations. |
17:00 |  | Keynote Presentation Organoids, A Preclinical Patient Population
Robert Vries, CEO, HUB Organoids, Netherlands
Key to the improvement of drug development and disease modeling is a preclinical model that represents patients. We previously developed an adult stem cells derived culture system that allowed for the genetically and phenotypically stable expansion of human epithelial cells. The Organoids derived from a variety of organs such as lung, liver, pancreas, breast, etc, are a powerful tool to study Cancer, Cystic Fibrosis and other diseases. Recent studies show that the in vitro response to drug treatments tested organoids correlate with the clinical outcome of the patient from which the organoid was derived. Therefore, the organoids appear to faithfully represent a patient in the lab. The scalability of the organoids potentially provides a novel approach to screening in early discovery, drug development as well as predictive diagnostics. |
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17:30 | Industry Panel Discussion Focusing on 3D-Culture and Organoids
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18:15 | Networking Reception with Beer and Wine -- Meet Colleagues and Network with New Acquaintances |
19:15 | Close of Day 1 of the Conference |
19:30 | 3D-Culture and Organoids Short Course Presented by Dr. Terry Riss [Separate Registration Required to Attend this Short Course] |
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