08:00 | Conference Registration, Materials Pick-Up, Morning Coffee and Pastries |
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Session Title: Opening Plenary Session | Session Sponsors |
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09:00 |  | Keynote Presentation Integration of Systems Biology with Organs on Chips for Disease Modeling and Drug Development
Linda Griffith, Professor, Massachusetts Institute of Technology (MIT), United States of America
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09:30 |  | Keynote Presentation Fitting iPSCs, 3D Cell Culture, Tissue Chips and Microphysiological Systems into the Grand Scheme of Biology, Medicine, Pharmacology, and Toxicology
John Wikswo, Gordon A. Cain University Professor, A.B. Learned Professor of Living State Physics; Founding Director, Vanderbilt Institute for Integrative Biosystems, Vanderbilt University, United States of America
As the engineering supporting body-on-chip (BoC) studies advances and
begins to penetrate both science and industry, we need to explore three
separate multidimensional spaces – one that spans BoC components, one
that covers the analytical techniques to characterize BoC performance
and drug response, and a third that spans the fields of application.
The component technologies being brought together include induced
pluripotent stem cells (iPSCs), 3D cell culture (which is beginning to
involve vascularization), tissue-chip bioreactors that enable the
recreation to tissue-like microenvironments, and the hardware required
to operate coupled microphysiological systems in a manner that
recapitulates human physiology and its response to drugs and toxins. The
second, analytical space is only now coming to the fore. To date, most
tissue-chip studies have reported morphological features, the expression
of small sets of genes, or the secretion of a few, organ-specific
compounds. A much more comprehensive battery of techniques is already in
regular use in the pharmaceutical industry, including genomics,
proteomics, and transcriptomics. Metabolomics is rapidly moving into
prominence as the instrumentation improves and the databases expand.
What is needed, though, are comprehensive comparisons between in vitro
and in vivo studies, as has been recently demonstrated with a weighted
gene coexpression network analysis that compare rat liver in vivo with
both mouse liver in vitro and rat primary hepatocytes growing in a dish,
which showed that a mouse liver was a better model of the rat liver
than the primary rat hepatocytes in a dish, which more closely resembled
a rat liver exposed to a significant toxic load. The BoC community
needs to compare, for example, a mouse with a mouse-on-a-chip to confirm
that the appropriate physiology is being recapitulated. The final space
spans biology, medicine, pharmacology, physiology and toxicology. BoCs
offer, for the first time, the ability to recreate in vitro and in
parallel, with an ever-dropping cost, the effects of organ-organ
interactions. Nowhere will this be more important than in studies of
absorption, distribution, metabolism, and excretion - toxicity
(ADME-Tox), where one may need skin, lung, or gut to absorb a drug or
toxin, liver and kidney to metabolize and excrete drug metabolites and
toxins, adipose and muscle tissue to store metabolites and toxins, and a
means to characterize in depth the underlying processes and how they
affect the chosen target organs. BoCs will thereby contribute not only
to toxicology, but our fundamental understanding of cellular biology and
systems physiology, thereby advancing both pharmacology and medicine.
Given that we will never create a perfect microHuman BoC, we can use
these three spaces to guide the compromises we make as we create useful
models, even toy models, of human physiology. |
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10:00 |  | Keynote Presentation Engineered Living Systems: Current State and Future Potential
Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT), United States of America
Following on recent advances in understanding single cell behavior (Carrera & Covert, Trends in Cell Biology, 2015), and in developing simple, proof-of-concept biological machines (Raman et al., PNAS, 2015, Park et al., Science, 2016), organoids (Fatehullah et al, Nature Cell Biology, 2016), and organ-on-chip technologies (Huh, et al., Science, 2010), efforts are underway to standardize manufacturing methods for engineered living systems (ELS). The approaches proposed, however, are widely divergent and often lack a sound basis due to the absence of a fundamental understanding of aspects unique to ELS – e.g., complexity, the central role of emergence – and fail to take advantage of their extraordinary capabilities – self-assembly, growth, self-repair, adaptation, learning.
We need to build on our current knowledgebase for the development and design of ELS, rethinking much of what we have learned from abiotic engineered systems. A major effort is therefore required to characterize, model and image the dynamical behavior of ELS, and thus establish the design principles needed for robust manufacture. While many ELS can survive merely by diffusion of gases and nutrients from their environment, most systems exceeding several hundred microns in lateral dimension require some means for convective transport, such as the circulatory system found in many living organisms. Several approaches have been employed to meet these needs, either by engineered conduits or induced network growth from seeded or suspended cells. In this talk, some of these methods will be described, focusing on networks that form by self-assembly, tend toward a stabilized perfusable network within 1-2 weeks, synthesize and organize their own matrix environment, and adapt to changing conditions. Both the successes and challenges of creating these networks will be discussed with the aim of developing reliable, vascularized ELS amenable to biomanufacture. |
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10:30 | Coffee Break and Networking in the Exhibit Hall |
11:00 |  | Keynote Presentation Human “Body-on-a-Chip” Systems to Test Drug Efficacy and Toxicity
Michael Shuler, Samuel B. Eckert Professor of Engineering, Cornell University, President Hesperos, Inc., United States of America
Human microphysiological or “Body-on-a-Chip” systems are powerful tools to assess the potential efficacy and toxicity of drugs in pre-clinical studies. Having a human based, multiorgan system, that emulates key aspects of human physiology can provide important insights to complement animal studies in the decision about which drugs to move into clinical trials. Our human surrogates are constructed using a low cost, robust “pumpless” platform. We use this platform in conjunction with “functional” measurements of electrical and mechanical activity of tissue constructs (in collaboration with J. Hickman, University of Central Florida). Using a system with four or more organs we can predict the exchange of metabolites between organ compartments in response to various drugs and dose levels. We will provide examples of using the system to both predict the response of a target tissue as well as off-target responses in other tissues/organs. We believe such models will allow improved predictors of human clinical response from preclinical studies. |
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11:30 |  | Keynote Presentation Human Emulation System: an Organs-on-Chips Platform for Advancing Drug Discovery and Development
Katia Karalis, Executive Vice President of Research, Emulate, Inc., United States of America
Micro-engineered Organs-on-Chips show physiological functions consistent with normal living human or animal cells in vivo. Each Organ-Chip is composed of a clear flexible polymer about the size of a AA battery that contains hollow channels lined by living human cells. The cells are cultured under continuous flow and mechanical forces thereby recreating key factors known to influence cell function in vivo. Cells cultured under continuously perfused, engineered 3D microenvironments go beyond conventional 3D in vitro models by recapitulating in vivo intercellular interactions, spatiotemporal gradients, vascular perfusion, and mechanical microenvironments. Integrating cells within Organs-on-Chips, enables the study of normal physiology and pathophysiology in an organ-specific context. Cellular/molecular level resolution is enhanced and demonstrates key insights into the mechanisms of action of drug induced toxicity. Numerous recent advances in applications of these systems are relevant in drug discovery/development for compound selection, and in de-risking mechanistic concerns using various organ systems. In this presentation we will highlight studies from collaborative efforts across our Human Emulation System with various academic and industry partners to demonstrate the utility of the system as a more predictive human-relevant alternative for efficacy and safety testing of new chemical entities in humans. |
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12:00 |  | Keynote Presentation Novel Microphysiological Multi-Organ Systems for Studies of Human Metabolic Diseases in Drug Discovery
Tommy Andersson, Drug Metabolism and Pharmacokinetics, Cardiovascular and Metabolic Diseases, AstraZeneca, Gothenburg, Sweden
Currently used pre-clinical models often suffer from poor translation of
drug responses to the patient due to the limited knowledge gained in
the efficiency and mode of action of the drug candidate. This
contributes to high attrition rates in early clinical programs. Multi
organ-on-a-chip emulating human physiology have the possibility to
improve success rate by mimicking the human disease state and improve
selection of the right targets and compounds early in drug discovery.
Such models will not only improve translation to patients but also
reduce time spent in early clinical programs as well as reducing the
needs for animal models. We developed a human liver - pancreatic islets
chip model. The model allows cross talk between cells from both organs
in a fluidic system and responds in a physiological way to glucose load
by increased insulin secretion leading to increased glucose consumption
(figure). Initial studies indicate that the model can become insulin
resistant and thus can be used as a metabolic disease model. Ongoing
studies are investigating how insulin resistance in liver cells effects
islet function by using the insulin receptor antagonists. |
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12:30 | Networking Lunch in the Exhibit Hall, Meet Exhibitors and View Posters |
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Session Title: The Deployment of iPSC-derived Cells for Drug Discovery |
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13:30 | .png) | Keynote Presentation Present (and Future) Uses for Stem Cells Derived Preparations in Drug Discovery and Toxicity Testing
Gary Gintant, Senior Research Fellow, Abbvie, United States of America
The advent of human pluripotent stem cells a decade ago sparked visions of novel screening approaches for drug safety and efficacy, narrowing the translational gap between traditional preclinical and clinical studies, and defining a new “proclinical space” where human derived preparations are used in preclinical assays. Not unlike other novel (and potentially disruptive) technologies, limitations learned along the way have provided new challenges for both the biology and technologies necessary for confident and efficient screening efforts. This presentation will highlight promising present and future applications for stem cell derived preparations, focusing on prospects for achieving translational success of new drug candidates. |
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14:00 |  | Keynote Presentation What’s Next for Stem Cells?
Devyn Smith, Chief Operating Officer, Sigilon, United States of America
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14:30 | Drug Testing on Patient-derived iPSC Cells
Bikash Pattnaik, M. D. Matthews Professor, McPherson Eye Research Institute, University of Wisconsin, Madison, United States of America
A presentation on disease modeling and drug testing using patient in a dish approach. |
15:00 | Complex Disease Genetics, Molecular Epidemiology, and the Power of iPSC-derived Cardiomyocytes
Ulrich Broeckel, Professor of Pediatrics, Medicine and Physiology - Chief, Section of Genomic Pediatrics, Medical College of Wisconsin, United States of America
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15:30 | Development of a Novel Drug Discovery Platform for Progressive Multiple Sclerosis
Stephen Crocker, Associate Professor, Department of Neuroscience, University of Connecticut School of Medicine, United States of America
Primary progressive multiple sclerosis (PPMS) is a chronic demyelinating disease of the central nervous system (CNS) without any effective treatment. Patients with PPMS generally do not benefit from currently prescribed immuno-modulatory therapies which can be effective among relapsing-remitting MS (RRMS) patients. Hence, promoting endogenous brain repair by promoting the differentiation of myelin-forming oligodendrocytes (OLs) is viewed as a potential strategy to halt and possibly restore neurologic function in patients with PPMS. This presentation will provide an update on our current approach to develop a novel drug screening assay that can be used to identify compounds with potential to promote brain regeneration in PPMS patients. The basis for this assay is our recently developed and characterized induced pluripotent stem (iPS) cell lines from PPMS patient samples which we have determined can be used to model the lesion environment of the PPMS brain. When compared against iPS cells from age-matched, non-diseased control cell lines we recently reported that the cells from all PPMS patients tested have an inherent defect in their ability to protect or promote myelin forming OLs. This work provides an innovative approach with personalized medicine potential because it models a crucial aspect of the disease microenvironment. Outcomes from this assay may have important implications for understanding re-myelination failure in PPMS that may have therapeutic potential to benefit other forms of MS. |
16:00 | Leveraging Novel Technologies for Human iPSC-based Screening
Xianmin Zeng, Associate Professor, Buck Institute for Research on Aging, United States of America
Human induced pluripotent stem cell (iPSC) technology offers the benefits of a cell line coupled with the advantage of using human primary cells. We have developed a panel of iPSC lines for neurotoxicity assays and disease modeling. These include: 1) control lines, 2) patient-specific lines, 3) lineage-specific knock-in reporters, 4) isogenic controls of single and double knock-outs. We have also established scalable protocols for generating differentiated cells in an assay ready format. I will discuss the utility of these lines for neurotoxicity assays including assays to determine the specificity of different neural cell types for a small range of chemicals and drugs from the Tox21 library, as well as for neuroprotective assays with dopaminergic neurons. |
16:30 |  | Keynote Presentation 3D Cell-Material Micro-Tissue Devices in Application of ES/iPS Cells for Drug Screening/Toxicology and Cell Therapy
Norio Nakatsuji, Chief Advisor, Stem Cell & Device Laboratory, Inc. (SCAD); Professor Emeritus, Kyoto University, Japan
SCAD is a start-up company founded in 2014 based on the integration of stem cell technology and nanotechnology/micro-engineering developed at Kyoto University. We are currently focusing on the iPSC-derived cardiomyocytes, with possible addition of neurons and hepatocytes. Cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) are promising materials for drug screening/toxicology and cell therapy. However, there are two major issues: immaturity of hPSC-CMs and instability of cardiac cellular function. To overcome these issues, we use two technologies: the robust cardiac differentiation method and aligned nanofibers as a culture scaffold. Our cardiac differentiation method can efficiently generate cardiomyocytes from any hPSC lines under cytokine-free defined condition. The hPSC-CMs seeded on nanofiber scaffolds formed 3D multilayered structures (Micro-Tissues), which show upregulated expression of cardiac maturation marker genes and enhanced and stable cardiac cell functions. Our micro-tissue devices are easy to handle and highly useful for drug screening/toxicology assays. |
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17:00 |   | Moderator Fireside Talk: Fusing Microphysiological Systems and Systems Biology Toward Fulfilling Their Promise
Emma Sceats, Chief Executive Officer, CN Bio Innovations Ltd.
Douglas Lauffenburger, Professor/Head, Massachusetts Institute of Technology, United States of America
This fireside talk will examine advances in the field of systems biology and how the marriage of computational systems biology and microphysiological systems will be of significant importance to progress in both of these fields during the next decade.
Beer and Wine will be served during this fireside talk to facilitate networking and engagement. |
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18:00 | Networking Cocktail Reception with Beer, Wine and Appetizers. Enjoy the Boston Skyline, Engage with Colleagues and Discuss Collaborations and Partnerships |
19:30 | Close of Day 1 of the Conference |
19:45 | Dinner Short Course on 3D-Culture [Separate Registration Required] |
