Inadequate representation of the human tissue environment during a preclinical screen can result in inaccurate predictions of compound effects. Thus, pharmaceutical investigators are searching for preclinical models that closely resemble original tissue
for predicting clinical outcome. Three-dimensional cell culture recapitulates normal and pathological tissue architectures that provide physiologically relevant models to study normal development and disease. However, challenges remain for high-throughput
screening as researchers must procure large numbers of identical 3D cell cultures, develop assays and obtain fast, automated readouts from these more complex assays. Join cell biologists, tissue engineers, assay developers, screening managers and
drug developers at Cambridge Healthtech Institute’s second annual 3D Cellular Models: Revitalizing Phenotypic Screening conference as they discuss strategies that accelerate the identification of novel therapeutic leads.
Thursday, June 16
11:00 am Registration
12:00 pm BRIDGING LUNCHEON PRESENTATION: Case Studies in Cardiac and Neuro Safety / Toxicity Assessment Using Human iPSC-Derived Cell Systems
Greg Luerman, Ph.D., Head, Applications Development, Axiogenesis Inc
A major challenge in drug development is identifying novel cellular tools that more accurately reflect human biology while providing a significant advance over current methods. Here we provide several snapshots/case studies that utilize human induced pluripotent stem cell-derived cardiomyocytes and neurons. These cells provide a flexible, high value human cellular system that offer a highly translational and typically more predictive cellular environment than immortalized cell lines or even primary rodent models.
12:30 Session Break
1:00 Coffee and Dessert in the Exhibit Hall with Poster Viewing
1:45 PLENARY KEYNOTE SESSION
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Chairperson’s Opening Remarks
Mahmud Bani, Ph.D., Team Leader, Senior Research Officer, Translational Bioscience, National Research Council Canada
»4:25 KEYNOTE PRESENTATION: OVERCOMING THE CHALLENGES OF QUANTITATIVE HIGH-THROUGHPUT CONFOCAL MICROSCOPY OF 3D SPHEROIDS
Jeffrey Morgan, Ph.D., Professor, Medical Science, Department of Molecular Pharmacology,
Physiology and Biotechnology, Brown University
Multicellular 3D spheroids are providing far more biological complexity than standard 2D monolayer cell culture. There is growing excitement for the use of spheroids in phenotypic drug discovery and the development of more predictive models of
toxicity. However, unlike thin 2D monolayers that are easily imaged, there are significant challenges to quantitative confocal imaging of spheroids. This talk addresses these challenges as they pertain to quantitative high-throughput confocal
4:55 3D Cell Culture with the RAFT™ Cell Culture System and Next-Generation Cell-Based Assays
Gregory Alberts, Ph.D., Global Subject Matter Expert, Lonza
The RAFT™ 3D Culture System uses a collagen matrix at physiologically relevant concentrations to more effectively mimic the in vivo situation. Because of the unique way that RAFT cultures are created, additional epithelial or endothelial cell
overlays may be added to create co-cultures or more complex cultures. In addition, the RAFT™ Technology can be combined with the Lonza Nucleofector™ System, iPSC-generation, and CRISPR/Cas9-based genome editing to generate next-generation
5:10 Sponsored Presentation (Opportunity Available)
5:25 Bioengineered 3D Tissue and Tumor Models for Drug Screening and Personalized Medicine
Aleksander Skardal, Ph.D., Assistant Professor, Wake Forest Institute for Regenerative
Medicine, Wake Forest School of Medicine
5:55 Computational Modeling – Driven Design of 3D-Printed Tissue-on-a-Chip Microfluidic Devices Used as Drug Screening Platforms
Filippos Tourlomousis, Research Assistant, Mechanical Engineering,
Stevens Institute of Technology
The dynamic nature of in vitro drug screening models demands reliable numerical tools to determine key design parameter values towards high-fidelity 3D cell-based platforms for drug metabolism and permeability studies. These in silico tools can furnish a priori information concerning cellular mechanotransduction to guide biologically inspired engineering design of microdevices. We illustrate computational methods’ importance toward design of more physiologically
relevant devices via a dynamic in vitro liver-on-chip and blood-brain barrier device.
6:25 Close of Day
6:30 Dinner Short Course Registration
7:00 - 9:30 Dinner Short Courses
Friday, June 17
7:15 am Registration
7:30 Interactive Breakout Discussion Groups with Continental Breakfast
This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas
and active networking. Continental breakfast is available for all participants.
Topic: The Importance of the Tanycyte Barrier at the Median Eminence: An “Open Brain Window” to the Metabolic Hypothalamus
Filippos Tourlomousis, Research Assistant, Mechanical Engineering, Stevens Institute of Technology
- Tanycytes in the median eminence are stem cells. What mechanisms control the proliferation of tanycytes?
- What is the effect of the hydrodynamics in the median eminence and the third ventricle on the barrier’s “tightness”?
- Would an in vitro tanycyte barrier model be useful for the pharmaceutical industry?
Topic: In vitro Models of Human Stem Cells with CNS Applications
Mahmud Bani, Ph.D., Team Leader and Senior Research Officer, Translational Bioscience, National Research Council Canada
- Selection and expansion of stem cell clones in vitro
- Using stem cell cultures for phenotypic and target-based screening in the CNS
- Developing brain organoids for cellular, molecular and pharmacological assays
- Stem cell-based brain-on-a-chip: concept, applications and challenges
- CNS disease models in a dish: opportunities and challenges
Topic: 3D Bioprinting in Tissue Engineering and Regenerative Medicine
Xiaofeng Cui, Ph.D., Professor & Department Chair, Department of Life Sciences and Technology, Wuhan University of Technology; Vice President, Research & Development, Stemorgan Therapeutics
- Bioprinting approaches
- Tissue bioprinting
- Translating bioprinting to clinic
Topic: Tools for Recapitulating the in vivo Microenvironment in 3D Cell Culture Models
Jeffrey T. Borenstein, Ph.D., Laboratory Technical Staff, Biomedical Microsystems, Draper Laboratory
- Microscale topographic patterning and matrix technology for organ models
- Fluid control technology for circulation, organ perfusion, and organ crosstalk
- Embedded sensor technologies for real-time monitoring of organ models
- Mimicking dynamic processes in organ models
8:35 Chairperson’s Remarks
Jeffrey Morgan, Ph.D., Professor, Medical Science, Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University
»8:45 KEYNOTE PRESENTATION: DESIGNING 3D TISSUE MODELS OF HUMAN SKIN DISEASE: FROM IPSC TO CRISPR
Jonathan Garlick, D.D.S, Ph.D., Professor, School of Dental Medicine, Tufts University;
Director, Division of Cancer Biology and Tissue Engineering, Tufts School of Medicine, School of Engineering and Sackler School of Graduate Biomedical Sciences
When combined with emerging technologies, such as gene editing and iPSC reprogramming, 3D tissue models offer unique platforms that mimic the complex microenvironments in which human disease develops. This talk describes the development of 3D,
skin-like tissues that incorporate iPSC-derived cells and cells modified by CRISPR-Cas9 that model non-healing diabetic wounds and Scleroderma. These “disease in a tissue” platforms can now accelerate the translation of in vitro findings into clinical applications.
9:15 Quantitative High-Throughput Screening Using a Primary Human 3-Dimensional Organotypic Culture Predicts in vivo Efficacy
Madhu Lal-Nag, Ph.D., Group Leader, Trans-NIH RNAi Facility, National Center for Advancing Translational
Sciences, National Institutes of Health
Two-dimensional cell cultures cannot recapitulate the issues of drug gradients, drug perfusion and the effects of hypoxia. Increasing evidence attests to the fact that gene expression signatures and the regulation of various signaling pathways are
dependent on various cues from the tumor microenvironment. In vitro model platforms that are designed to be biologically relevant fill a critical gap between the cellular and animal model domains and offer the opportunity to study, screen
and select compounds that are therapeutically attractive in real time.
9:45 Organ Bioprinting, Are We There Yet?
Xiaofeng Cui, Ph.D., Professor & Department Chair, Department of Life Sciences and Technology,
Wuhan University of Technology; Vice President, Research & Development, Stemorgan Therapeutics
We have had more than a decade to investigate bioprinting technology: whether we can print cells, tissues, or even organs. So far we have answered many questions, but we are also facing more and more questions. Is bioprinting just a tool for basic
research or a groundbreaking technology which will eventually change human life? Here we discuss the present and future of bioprinting.
10:15 Coffee Break in the Exhibit Hall. Last Chance for Poster Viewing.
11:00 3D Cellular Models for Therapeutic Target Discovery
Aron Jaffe, Ph.D., Senior Investigator, Regenerative Medicine Hub Leader, Developmental and Molecular
Pathways, Novartis Institutes for BioMedical Research
High-throughput screening of immortalized or tumor cell lines grown on plastic is widely used to identify potential therapeutic targets. However, these methods fail to recapitulate many features of multicellular tissue architecture found in vivo,
which have profound effects on a variety of cell behaviors. This presentation highlights the strategies for designing complex (3D) cellular assays for target discovery using medium and high-throughput screening methods.
11:30 Using in vitro Models of Human-Induced Pluripotent Stem Cells for Drug Screening
Mahmud Bani, Ph.D., Team Leader, Senior Research Officer, Translational Bioscience, National Research
Recent advances in cell reprogramming have enabled the generation of induced pluripotent stem cells (iPSC) as renewable sources of cells for a wide range of applications in drug discovery and cell-based therapies. Our laboratory has established several
iPSC lines from human amniotic fluid cells, and differentiated them into various phenotypes. We show that 2D and 3D iPSC models can serve as complementary tools to evaluate drug candidates in preclinical stages.
12:00 pm Development of Biologically Relevant Three-Dimensional Solid Tumor Models for Target Validation and Compound Screening
Jason Ekert, Ph.D., Senior Research Scientist, Biologics Research, Janssen BioTherapeutics
Development of biologically relevant in vitro models to better mimic the tumor microenvironment for solid tumors need to be established so drug targets can be better characterized. We have established multiple high-content imaging-based 3D
tumor models for evaluating biologics and other novel therapeutic platforms. The tumor models should allow for a more informed characterization of drug candidates.
12:30 Luncheon Presentation: Long-Term Monitoring of Tumor Spheroids in Treatment Testing: Rationale, Challenges and Semi-Automation
Leoni Kunz-Schughart, Ph.D., Professor, Tumor Pathophysiology, OncoRay, National Center for Radiation Research in Oncology
The lecturer’s group has used spheroids/spheres and 3-D co-cultures over the past 25 year in different academic environments to study tumor pathophysiological phenomena in vitro and as platform for combinatorial anti-cancer therapy testing
with short- and long-term analytical endpoints. The presentation will particularly highlight the challenge of standardization and semiautomation in spheroid handling by giving an overview as well as specific examples for the utilization of
an automated pipetting device.
1:00 Session Break
1:30 Chairperson’s Remarks
Murat Cirit, Ph.D., Director, Translational Systems Pharmacology, DARPA-PhysioMimetics Program, Massachusetts Institute of Technology
1:35 Biological Studies: On-Chip Fabrication and Characterization
Nastaran Hashemi, Ph.D., Assistant Professor, Department of Mechanical Engineering,
College of Engineering, Iowa State University
I discuss two areas of research in our lab. Polymer fibers have been increasingly used in tissue engineering applications since they provide cells with a hydrated 3D microenvironment that mimics the native extracellular matrix. We have employed
hydrodynamic focusing and solvent extraction to fabricate highly structured biocompatible and biodegradable polymer microfibers in a microfluidic platform. We have also developed approaches to merge microscale techniques for biological studies
and cell-based screening.
2:05 Strategies for Integrating 3D Tissue Systems into Multi-Organ Platforms
Collin Edington, Ph.D., Research Scientist, Linda Griffith Laboratory, Biological
Engineering, Massachusetts Institute of Technology
Many current 3D tissue models are developed with little or no consideration of downstream integration with other systems. Managing the interplay of tissue scale, fluidic architecture, and media composition (among many factors) is critical to maintaining
healthy cultures and understanding the interactions of these multi-organ models.
2:35 The Patent Landscape of Organs-on-a-Chip
Stephanie Elmer, Ph.D., J.D., Associate, Biotechnology and Chemical Group, Sterne, Kessler,
Goldstein & Fox
Should scientists who bioprint vessels and organs – objects that exist in nature – be able to patent these technologies? Patenting bioprinting techniques has quietly been happening for years. Yet the interplay between these technologies
and current patent laws is unclear and ripe for examination by the courts. This presentation highlights the three process phases of bioprinting, exceptions to patent infringement for experimental uses, and prospects for further patenting and
patent infringement lawsuits.
3:05 Refreshment Break
3:20 Engineering Challenges for Organ-on-Chip Scalability: Can High Content and High-Throughput Screening Both Be Achieved?
Luke MacQueen, Ph.D., Research Scientist, Disease Biophysics Group, Wyss Institute for
Biologically Inspired Engineering; John A. Paulson School of Engineering and Applied Sciences, Harvard University
This talk summarizes challenges facing organ-on-chip (OOC) technology development. As a nascent multidisciplinary field, OOC platform developers face open questions in multiple scientific disciplines, including biology, material science, and manufacturing.
Using illustrative examples from our laboratory, focusing on cardiac OOCs, we discuss organ scaling, inter-organ coupling, OOC instrumentation, manufacturing and quality control. We aim to identify strategies that improve OOC basic science
and translation to preclinical research.
3:45 Microfluidic Technologies for Multiplexed and Interacting Organ Models
T. Borenstein, Ph.D., Laboratory Technical Staff, Biomedical Microsystems, Draper Laboratory
Here we present recent progress in the development of microfluidics-based approaches for multiplexed and interacting dynamic organ models. Flow control, critical to organ perfusion, media circulation, establishment and maintenance of gradients
and pharmacokinetic profiles, and governing organ crosstalk, is a central challenge for the field. The onboard flow control technologies described here are shown to provide precise and reliable operation over extended periods in multiplexed
and interconnected organ model systems.
4:10 Organs-on-Chips: Advances in Microphysiological Systems and Application for Disease Modeling and Drug Testing
Remi Villenave, Ph.D., Principal Investigator/R&D Lead, Emulate, Inc.
Organs-on-Chips are miniaturized 3D cellular models of human tissues that replicate the smallest functional unit of an organ and recreate how organs work in the body and how disease processes occur. They can be used to improve our understanding
of human biology or refine how we test drugs. We present the latest advances in Organs-on-Chips technology with emphasis on the Lung Alveoli-on-Chip and the recently published Lung Airway-on-Chip.
4:35 Human Physiome-on-a-Chip: A Platform for Drug Discovery and Development
Murat Cirit, Ph.D., Director, Translational Systems Pharmacology, DARPA-PhysioMimetics Program, Massachusetts
Institute of Technology
The simplicity of conventional in vitro models makes them incapable of achieving adequate physiological relevance for mimicking the human body, a dynamic system that has complex three-dimensional microenvironment, intracellular communications
and organ interactions. Hence, there is an urgent need to develop more physiologically relevant in vitro systems for better simulating the human body in response of drugs and providing more reliable in vitro-in vivo translation (IVIVT) from preclinical results to clinical outcomes.
5:00 Close of Conference