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SELECTBIO Conferences 3D-Models for Drug Testing: Organoids & Tissue Chips 2022

3D-Models for Drug Testing: Organoids & Tissue Chips 2022 Agenda



Co-Located Conference Agendas

Extracellular Vesicles 2022: Biology, Disease & Medicine | 3D-Models for Drug Testing: Organoids & Tissue Chips 2022 | 

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Tuesday, 13 September 2022

08:00

Conference Registration, Materials Pick-Up, Morning Coffee and Tea


Session Title: Conference Opening Session -- Organoids and Tissue Chips Status 2022

09:00

Albert FolchConference Chair

Tumor-on-a-Chip Platforms for High-Fidelity Cancer Drug Testing Using Intact Tumor Biopsies
Albert Folch, Professor of Bioengineering, University of Washington, United States of America

Cancer remains a major healthcare challenge worldwide. It is now well established that cancer cells constantly interact with fibroblast cells, endothelial cells, immune cells, signaling molecules, and the extracellular matrix in the tumor microenvironment (TME). Present tools to study drug responses and the TME have not kept up with drug testing needs. Oncology drugs typically take 10 years and cost an average of 1 billion dollars to develop. The number of clinical trials of combination therapies has been climbing at an unsustainable rate, with 3,362 trials launched since 2006 to test PD-1/PD-L1-targeted monoclonal antibodies alone or in combination with other agents. We have developed a microfluidic platform (called Oncoslice) for the delivery of multiple drugs with spatiotemporal control to live tumor biopsies, which retain the TME. We have developed the use of Oncoslice for the delivery of small-molecule cancer drug panels to glioblastoma (GBM) xenograft slices as well as to slices from patient tumors (GBM and colorectal liver metastasis). In addition, we have developed a precision slicing methodology that allows for producing large numbers of cuboidal micro-tissues (“cuboids”) from a single tumor biopsy. We have been able to trap cuboids in arrays of microfluidic traps in a multi-well platform. This work allows for multiplexing the application of drugs to human tumor tissues in a format that maintains the TME intact.

09:30

John RogersKeynote Presentation

3D Mesoscale Structures as Bioelectronic Interfaces to Cortical Spheroids
John Rogers, Simpson/Querrey Professor of Materials Science and Engineering, Northwestern University, United States of America

Three-dimensional (3D), sub-millimeter-scale collections of neural cells, known as cortical spheroids and organoids, are of rapidly growing importance in neuroscience research due to their ability to reproduce complex features of brain architecture, function and organization in vitro. Despite their great potential for studies of neurodevelopment, neurological disease modeling and evolution, these miniaturized, fragile 3D living biosystems cannot be examined easily using conventional methods for neuromodulation, sensing and manipulation.   This talk describes an unusual 3D neurotechnology platform that can be tailored with shapes, sizes and complex geometries that match those of individual organoids/spheroids and small collections of them, sometimes referred to as assembloids. Systematic studies demonstrate various electrical, thermal, chemical and optical modes of operation that can be supported by these frameworks, including examples of their use in monitoring electrophysiological behaviors across the surfaces of healthy human stem cell derived cortical spheroids and in examining processes of neuroregeneration between lobes of transected assembloids formed from pairs of spheroids.

10:00

Constructing Organ-Specific Microvasculature for Disease Modeling and Regeneration
Ying Zheng, Associate Professor, Department of Bioengineering, University of Washington, United States of America

Engineered tissues have emerged as promising new approaches to repair damaged tissues as well as to provide useful platforms for drug testing and disease modeling. Challenges remain to reconstruct organ-specific vasculature and tissue environment for disease modeling. Here I will present our progress in generating complex vascular structure with large range of diameters and curvatures, by combining multiple fabrication tools, to support its remodeling, thick tissue growth and blood perfusion. I will present means to study organ-specific vascular structure and function. Finally I will summarize the remaining challenges and perspective in exploiting engineering tools to advance our understanding of biology and medicine.

10:30

Title to be Confirmed.
Ali Khademhosseini, CEO and Founding Director, Terasaki Institute for Biomedical Innovation, United States of America


Mid-Morning Coffee, Tea and Networking in the Exhibit Hall

11:30

Microengineering of Organotypic Tissue On-Chip Technologies for Disease Modeling Applications
Mehdi Nikkhah, Associate Professor of Bioengineering, Arizona State University, United States of America

Development of ex vivo three-dimensional (3D) biomimetic tissue models has gained significant attention for variety of applications in biomedical and clinical research. Tissue on-chip technologies have enabled addressing the limitations of animal models to better understand the biological mechanisms of complex diseases in humans, such as cancer. These technologies have also immensely facilitated the process of drug development and discovery through creating scalable and high-throughput miniaturized platforms, to test the efficacy of multiple compounds in an efficient manner. In this seminar, Dr. Nikkhah will present the multidisciplinary research focus of his laboratory on the integration of advanced biomaterials, microscale technologies, and biology to develop the next generation of physiologically relevant and organotypic tissue on-chip platforms for disease modeling applications. Specific emphasis in this seminar will be placed on engineering of tumor microenvironment (TME) models to study cancer progression at the earliest stages of the metastatic cascade. In addition, he will also discuss the development of 3D human stem cell-derived heart on-a-chip model to study cardiovascular diseases.

12:00

Spatially Organized Microfluidic Models of the Lymph Node Ex Vivo
Rebecca Pompano, Associate Professor, Carter Immunology Center, University of Virginia, United States of America

Adaptive immunity begins in the lymph node, a small yet highly structured organ that has proven difficult to model with standard in vitro approaches.  The intricate spatial organization and dynamic nature of cell migration through this organ traditional interface-focused organ-on-chip models of limited use.  We have developed an approach that combines intact ex vivo slices of lymph node tissue with microfluidic fluid flow control, to begin to reproduce organ-level events in this fascinating tissue.  Tissue slices retain the spatial organization of the tissue and are readily adopted by biomedical research laboratories.  Using single-tissue cultures as well as multi-organ microfluidic cultures, we have established models of draining lymph node interactions with tumors and with vaccinated skin or muscle. Ultimately, these tools will be useful to visualize where, when, and how cells interact during immunity and inflammation, to reveal mechanisms of the immune response and inform the development of vaccines and immunotherapies.

12:30

Networking Lunch in the Exhibit Hall with Exhibitors and Conference Sponsors

14:00

Cole DeForestKeynote Presentation

User-Programmable Hydrogel Biomaterials to Probe and Direct 4D Stem Cell Fate
Cole DeForest, Weyerhaeuser Endowed Professor , University of Washington, United States of America

The extracellular matrix directs stem cell function through a complex choreography of biomacromolecular interactions in a tissue-dependent manner. Far from static, this hierarchical milieu of biochemical and biophysical cues presented within the native cellular niche is both spatially complex and ever changing. As these pericellular reconfigurations are vital for tissue morphogenesis, disease regulation, and healing, in vitro culture platforms that recapitulate such dynamic environmental phenomena would be invaluable for fundamental studies in stem cell biology, as well as in the eventual engineering of functional human tissue. In this talk, I will discuss some of our group’s recent successes in reversibly modifying both the chemical and physical aspects of synthetic cell culture platforms with user-defined spatiotemporal control, regulating cell-biomaterial interactions through user-programmable Boolean logic, and engineering microvascular networks that span nearly all size scales of native human vasculature (including capillaries). Results will highlight our ability to modulate intricate cellular behavior including stem cell differentiation, protein secretion, and cell-cell interactions in 4D.

14:30

Matthias von HerrathKeynote Presentation

Human Type 1 Diabetes On-a-Chip
Matthias von Herrath, Vice President and Senior Medical Officer, Novo Nordisk, Professor, La Jolla Institute, United States of America

Over the past years we have engineered an in vitro system that can replicate key aspects we have seen in human type 1 diabetes pathogenesis. We will demonstrate the system's utility, notably that the readout is very sensitive in respect to beta cell function (glucose induced insulin secretion), rather than cell death. In addition the readout, due to the uniform islet spheroid size, is highly standardized.  This system can be helpful in understanding which factors and pathways are key for beta cell destruction and their relative importance. It is also useful in evaluating the ability of beta cell targeted therapies to lower the immune attack.

15:00

Steven C. GeorgeKeynote Presentation

Using Microfluidics For Immune Cell Trafficking and Capture
Steven C. George, Professor and Chair, Department of Biomedical Engineering, University of California-Davis, United States of America

Microfluidic technology has played a leading role to advance our understanding of fundamental biological processes including cell separation and isolation, next generation sequencing, and cell trafficking.  Over the past five years our lab has applied the basic principles of microfluidics to control fluid shear and flow to create simple microphysiological systems to better understand:  1) how to capture and isolate rare immune cells from the peripheral circulation, and 2) the principles which guide and control immune cell (lymphocytes, monocytes, and neutrophils) trafficking in complex tissue microenvironments.  For the former, we leverage the ability to coat surfaces with antigens that are recognized by rare populations of B lymphocytes in the peripheral circulation.  We then control the shear force at the surface and can capture and isolate these rare cell populations.  Understanding how these rare cell populations evolve over time following viral (e.g., SARS-Cov2, influenza) infection is central to understanding immunity following infection or immunization. For the latter, we are pursuing two projects.  The first involves neutrophil trafficking into the cardiac muscle during COVID19-induced “cytokine storm”, including counterstrategies that limit binding of neutrophils to the inflamed endothelium.  The second involves modeling myeloid cell-directed immunosuppression in the tumor microenvironment, and how counterstrategies, such as inhibiting PD-L1 or STAT3 signaling, can enhance CAR-T cell trafficking and effector function.  This talk will provide an overview of our major results from each of these projects.

15:30

Mid-Afternoon Coffee and Tea Break and Networking in the Exhibit Hall


Session Title: Conference Joint-Plenary Session

16:00

Nancy AllbrittonPlenary Presentation

Miniaturized Colon-on-Chip for Probiotic and Drug Screening
Nancy Allbritton, Frank and Julie Jungers Dean of the College of Engineering and Professor of Bioengineering, University of Washington in Seattle, United States of America

Organ-on-chips are miniaturized devices that arrange living cells to simulate functional subunits of tissues and organs. These microdevices provide exquisite control of tissue microenvironment for the investigation of organ-level physiology and disease. Planar models enable high throughput screening with primary human intestinal epithelial cells- both stem/proliferative cells and differentiated zones. Compound screening for stimulation or inhibition of hormone secretion by enteroendocrine cells is of high value for therapeutic development given the role that hormones and neurotransmitters such as glucagon-like peptide 1 and serotonin play in regulating human feeding behavior and metabolism. These simple models can also be adapted to produce a thick, functional mucus layer with or without an oxygen gradient to create an anaerobic luminal surface for culture of colonic flora. Such devices are high of value in evaluating the impact of probiotics- a growing therapeutic area for the treatment of human disease. These planar systems can be modified to produce “flat crypts” with a stem/proliferative zone and differentiated cell region for the study of stem cell proliferation, lineage allocation and migration. Fully 3D polarized epithelium possess an array of crypt-like structures replicating the intestinal architecture. Imposition of chemical gradients across the crypt long axis yields a polarized epithelium with a cell migration from a stem-cell niche into a differentiated cell zone. This in vitro human colon crypt array replicates the architecture, luminal accessibility, tissue polarity, mucus layer, cell types and cellular responses of in vivo intestinal crypts. These bioanalytical systems provide both high throughput as well as low throughput/content rich platforms for assay of microbiome-behavior, drug-delivery, and other assays with a living human intestinal epithelium.

16:30

Daniel ChiuPlenary Presentation

New Fluorescent Reagents to Enable Highly Multiplexed Single-Cell Measurements and Biological Assays
Daniel Chiu, A. Bruce Montgomery Professor of Chemistry, University of Washington, United States of America

Fluorescence based techniques have become an indispensible tool kit in both basic cellular studies and in vitro diagnostics. However, the intrinsic limitations of conventional dyes, such as short Stoke’s shift and low absorptivity, have posed difficulties for advancing highly multiplexed assays. We have developed a new class of fluorescent probes called Pdots, and this talk will highlight their development to enable high multiplex single-cell analysis and biological assays.

17:00

Danilo TaglePlenary Presentation

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.

18:00

Networking Reception with Beer and Wine: Network with Colleagues and Engage with Exhibitors and Conference Sponsors

19:00

Close of Day 1 Programming

Wednesday, 14 September 2022

08:00

Morning Coffee and Pastries in the Exhibit Hall


Session Title: Technologies and Approaches in the Organs-on-Chips Field

09:00

Using Organs-on-Chips for Screening Therapeutics for Pandemic Respiratory Infections
Jeffrey Borenstein, Group Leader, Synthetic Biology; Director, Biomedical Engineering Center, Draper, United States of America

One of the most powerful applications of organs-on-chips is as a platform for generating human-relevant data in screening therapeutic candidates across various disease models.  Here we present recent therapeutic screening results obtained using the high throughput human primary tissue culture platform PREDICT96-ALI (Air Liquid Interface) across pandemic respiratory infections including Influenza A Virus (IAV) and the coronaviruses hCoV-NL63, hCoV-OC43 and SARS-CoV-2.  These platforms, seeded with human primary tracheobronchial epithelial cells obtained from commercial sources as well as directly from bronchoscopies performed on living donors, enable rapid screening across a range of conditions including infection levels, cell source, candidate compound and therapeutic dose.  In the case of SARS-CoV-2, this represents a first demonstration of successful therapeutic screening in a high containment BSL-3 environment.  Results from the airway platform correlate closely with clinical data, demonstrating a compelling opportunity for an organ-on-chip model to serve a critical role in evaluating potential candidates capable of efficaciously treating severe respiratory infections.

09:30

Noo Li JeonKeynote Presentation

Title to be Confirmed.
Noo Li Jeon, Professor, Seoul National University, Korea South

10:00

Title to be Confirmed.
Kelly Stevens, Assistant Professor, Department of Bioengineering, University of Washington, United States of America

10:30

Mid-Morning Coffee, Tea and Networking in the Exhibit Hall

11:00

Title to be Confirmed.
Christopher Easley, Knowles Associate Professor, Auburn University, United States of America

11:30

Elisabeth VerpoorteKeynote Presentation

Title to be Confirmed.
Elisabeth Verpoorte, Professor of Analytical Chemistry and Pharmaceutical Analysis, University of Groningen, Netherlands

12:00

Roger KammKeynote Presentation

Title to be Confirmed.
Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT), United States of America

12:30

Networking Lunch, Meet Exhibitors and Engage with Colleagues

14:00

Microdissected Tissue Processing Using Open-Space and Closed Microfluidics – From First Principles Design to Drug Testing
Thomas Gervais, Professor of Engineering Physics and Biomedical Engineering, Ecole Polytechnique de Montréal, Canada

The inability to adequately predict the response of a given patient to therapeutic agents is a major, longstanding challenge in clinical oncology. In the past decade, there has been a major push to develop ex vivo platforms to directly probe the response of a patient’s tumor to a panel of drug candidates in order to optimize drug prescription and treatment response. Due to their small sizes, versatility and precise control of the culture microenvironment, microfluidics systems have emerged as a promising approach to develop such platforms. Yet, several challenges must be solved to ensure on-chip tumor viability, simplicity of use, throughput, and to deliver quality readouts for clinical decision making. In this talk, we will discuss the concept of micro-dissected tissue (MDT) as an emerging on-chip ex vivo model that is both simple to use, and compatible with current gold standard histopathology readouts. We will introduce two platforms, drawing upon classical and open-space microfluidics, for processing them and a general method to bridge the gap between MDT processing and gold-standard histopathology. Our results set the base for a complete micro-histological platform compatible with most solid tumour cancers, that provides the equivalent of tissue microarrays to assay individual response to drugs.


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