Next-Generation Organoid Cancer Models from the Human Cancer Models Initiative
James Clinton, Senior Scientist, American Type Culture Collection (ATCC)

ATCC is manufacturing and distributing models from The Human Cancer Models Initiative, an international consortium dedicated to generating hundreds of novel primary patient-derived cancer models, including three-dimensional organoids. These models can be propagated from cryopreserved material and are annotated with clinical and molecular data. HCMI models are intended as pre-clinical tools for disease modeling, biomarker identification, compound screening, and personalized medicine. These models hold promise to transform cancer research by being more physiologically relevant and predictive than existing in vitro models. In this presentation I provide an overview of the HCMI and ATCC’s involvement in making these novel cancer models available to the research community.

Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer
Hervé Tiriac, Assistant Researcher, University of California-San Diego, United States of America

New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for pancreatic cancer patients. Combined genomic, transcriptomic, and therapeutic profiling of patient-derived organoids can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses and facilitate precision medicine for pancreatic cancer patients.

Afternoon Coffee Break and Networking in the Exhibit Hall

From Brain Organoids to Animal Chimeras: Novel Platforms for Studying Human Brain Development and Disease
Abed Mansour, EMBO Fellow, The Salk Institute, United States of America

Due to the immense complexity of the human brain, the study of its development, function, and dysfunction during health and disease has proven to be challenging. The advent of patient-derived human induced pluripotent stem cells, and subsequently their self-organization into three-dimensional brain organoids, which mimics the complexity of the brain's architecture and function, offers an unprecedented opportunity to model human brain development and disease in new ways. However, there is still a pressing need to develop new technologies that recapitulate the long-term developmental trajectories and the complex in vivo cellular environment of the brain. To address this need, we have developed a human brain organoid-based approach to generate a chimeric human/animal brain system that facilitates long-term anatomical integration, differentiation, and vascularization in vivo. We also demonstrated the development of functional neuronal networks within the brain organoid and synaptic-cross interaction between the organoid axonal projections and the host brain. This approach set the stage for investigating human brain development and mental disorders in vivo, and run therapeutic studies under physiological conditions.

Versatile Synthetic Substrates For Cellular Assay Development and 3D Organoid Culture and Screening
Connie Lebakken, Chief Operating Officer, Stem Pharm, Inc., United States of America

Stem Pharm Inc. has developed a synthetic hydrogel platform that allows the design and optimization of substrates for cell expansion, differentiation and screening applications including 3D cell culture and organoid models. Through control of the substrate mechanical properties and adhesion ligand presentation, and utilizing chemistries that maintain cellular health and function, we provide cell-specific biomaterials for advanced cellular assay platforms and specialized cell expansion and differentiation applications.

Organoids as Emergent Systems Inducible by Designing the Adhesion Microenvironment of Stem Cells
Kennedy Okeyo, Senior Lecturer, Institute for Frontier Life and Medical Sciences, Kyoto University, Japan

The adhesion microenvironment plays important contributory roles in the induction of self-organized tissue formation and differentiation of pluripotent stem cells (PSCs). However, how the interaction with the surrounding physical microenvironment influences the complex processes of self-organization and differentiation which orchestrate organoid formation by stem cells remains to be fully understood. In this research, we are examining how the local adhesion microenvironment, as characterized by both cell-substrate and cell-cell adhesions, can trigger self-organization and differentiation globally, and lead to the emergence of higher-order structures such as organoids from lower-order cellular systems. To this end, we have developed a simple but versatile culture platform, namely, the micromesh culture technique which employs adhesion-limiting microstructured mesh substrates to modulate adhesion microenvironment and trigger self-organization of stem cells into ordered 3D structures in a manner which mimics tissue morphogenesis. This talk will highlight our recent findings that modulating the cell adhesion microenvironment by our culture technique can potentially trigger stem cells to exhibit differentiation and self-organization as seen in early embryogenesis, such as the emergence of the trophectoderm and primordial germ cells (PGCs), even under pluripotency maintaining culture conditions in vitro.

Application of Brain Model Technology
Alysson Muotri, Professor, Director of the Stem Cell Program, University of California-San Diego, United States of America

Brain organoids, generated from stem cells, have created opportunities to study morphological and molecular aspects of human neurodevelopment However, it is unclear if these organoids could generate sophisticated network activity. The Muotri lab has generated brain organoids with oscillatory waves similar to fetal stages of human development. Implications for human disease and brain evolution will be discussed.

Revolutionize Your Cancer Research With Next-Generation Models
Mindy Goldsborough, Chief Scientific Officer, ATCC

While current in vitro models for cancer have been the backbone upon which decades of research and discovery have been built upon, there still exists a need within the research community for more advanced models.  ATCC is tackling this challenge head-on.  Through both internal R&D, as well as participation in consortia such as the Human Cancer Models Initiative, ATCC is delivering a wide variety of next-generation cancer models to the research community. These advanced models include CRISPR gene edited cell lines and 3D models annotated with clinical and genomic data to promote rapid scientific advancements toward understanding, treating, and curing cancer.

Networking Reception with Beer, Wine and Dinner in the Exhibit Hall -- Sponsored by ATCC

Close of Conference Day

Morning Coffee, Pastries and Networking in the Exhibit Hall

3D Human Liver Spheroids for In Vitro Liver Toxicity Testing
Feng Li, Senior Scientist, Development, Corning Life Sciences

3D liver spheroids can be made from primary human hepatocytes (PHH) with or without other liver cell types. For 3D liver spheroid assay development, we have evaluated the impact of donor variations on spheroid formation and stability in vitro. Our results show that PHH lots need to be pre-tested for 3D spheroid culture and there exist variations in spheroid formation time and stability among different donor lots. Using a large set of 100 compounds, PHH liver spheroids are shown to significantly improve the prediction accuracy of drug induced liver toxicity comparing to conventional system. Furthermore, 3D spheroid culture qualified PHH can be used to generate co-culture liver spheroids with other liver cell types such as Primary human Kupffer cells. As 3D liver spheroid models are being adopted by more industry users, we’d like to share our experience working with liver spheroids and toxicity test results to facilitate a conversation on how to standardize 3D liver spheroid models for in vitro assays.

Progress in the Use of Human Stem Cells to Predict Developmental Neurotoxicity
Robert Halliwell, Professor of Neuroscience, University of The Pacific, United States of America

Current methods to assess the risks of damage to the developing nervous system from prenatal exposure to drugs rely heavily on animal models that are inefficient, costly and of poor predictive validity; there are also ethical concerns about using large numbers of animals in biomedical research. Ready availability of a variety of human stem cells and their potential to differentiate in to functional neurons (neurogenesis) is a powerful new platform to model development of the nervous system in a dish and to determine the impact of drugs and environmental agents on these processes. Our lab is investigating the potential of a variety of human stem cells to differentiate to functional neurons and glia and we are also examining their value to indicate (or predict) developmental neurotoxicity from a range of neuropsychiatric medicines. This presentation will provide new data from our lab on the impact of a range of anticonvulsant agents on stem cell viability, proliferation, neural differentiation and electrophysiological properties.

Morning Coffee Break and Networking in the Exhibit Hall

In Vitro Modeling of Neuromuscular Diseases Using Human Induced Pluripotent Stem Cells
Masatoshi Suzuki, Associate Professor, Department of Comparative Biosciences and Stem Cell & Regenerative Medicine Center, University of Wisconsin-Madison, United States of America

Neuromuscular diseases are caused by functional defects of skeletal muscles directly via muscle pathology or indirectly via the nervous system. Extensive studies have been performed to improve the outcomes of therapies; however, effective treatment strategies have not been fully established in any major neuromuscular disease. Human induced pluripotent stem cells (iPSCs) have a great capacity to differentiate into skeletal muscle progenitor cells (or know as myogenic progenitors) and skeletal myocytes for use in treating and modeling neuromuscular diseases. Further, recent innovations in bioengineering provide multifactorial and multidimensional controlled platforms for biomedical research beyond the traditional culture systems. Specifically, patient-derived iPSCs can be applied to differentiate into mature skeletal myotubes using newly featured cell culture systems such as two-dimensional (2D) skeletal-muscle-on-a-chip and three-dimensional (3D) skeletal muscle organoids. These bioengineering approaches can more closely mimic the native cellular environment and pathology in culture. Skeletal myotubes derived from patient-specific iPSC lines are a valuable resource for studying neuromuscular disease mechanisms and testing potential drug therapies.

Applications of Brain-Model Technology to Study Neuro-developmental Disorders
Cleber Trujillo, Project Scientist, University of California San Diego, United States of America

The complexity of the human brain permits the development of sophisticated behavioral repertoires, such as language, tool use, self-awareness, and consciousness. Understanding what produces neuronal diversification during brain development has been a longstanding challenge for neuroscientists and may bring insights into the evolution of human cognition. We have been using stem cell-derived brain model technology to gain insights into several biological processes, such as human neurodevelopment and autism spectrum disorders. The reconstruction of human synchronized network activity in a dish can help to understand how neural network oscillations might contribute to the social brain. Here, we developed cortical organoids that exhibit low-frequency network-synchronized oscillations. Periodic and highly regularized oscillatory network events emerged after 4 months, followed by a transition to irregular and spatiotemporally complex activity by 8 months, mimicking features of late-stage preterm infant electroencephalography. Furthermore, we found that the Methyl-CpG-binding protein 2 (MECP2) is essential for the emergence of network oscillations, suggesting that functional maturation might be compromised at early stages of neurodevelopment in MECP2-related disorders, such as Rett syndrome, autism, and schizophrenia. As evidence of potential network maturation, oscillatory activity subsequently transitioned to more spatiotemporally irregular patterns, capturing features observed in preterm human electroencephalography (EEG). These results show that the development of structured network activity in the human neocortex may follow stable genetic programming, even in the absence of external or subcortical inputs. Our model provides novel opportunities for investigating and manipulating the role of network activity in the developing human cortex.

Networking Lunch in the Exhibit Hall, Exhibits and Poster Viewing

The Use of Organotypic Liver Co-cultures for Use in Disease Modeling and Drug Development
Kenneth Brouwer, Vice President of Technology and ADME-TOX, BioIVT, United States of America

As the discovery and development of anti-fibrotic therapies still rely heavily on animal models, there remains an opportunity for robust and relevant in vitro models to support the identification and preclinical evaluation of potential new anti-fibrotic drugs. To this end, BioIVT has developed and characterized several human liver models which help to answer these questions.  The HEPATOPAC^® micropatterned hepatocyte co-culture and the 3D ORGANDOT^TM systems allow for the investigation of questions with increasing complexity and experimental duration.  In each case the incorporation of liver non-parenchymal fractions and extended culture time allow for better prediction of drug metabolism and disposition as well as disease model related endpoints.  For the ORGANDOT system, the inclusion of both Kupffer and stellate cells support the fibrotic phenotypic changes induced with TGFß1 treatment providing an in vitro model for anti-fibrotic drug efficacy.  We will report on data which demonstrates the broad utility in adding cellular and structural complexity to hepatocyte cultures as well as the optimization of endpoints including, molecular and immunohistochemical markers for the study of anti-fibrotic therapies.