Compared to traditional cell-based assay monolayers, three-dimensional (3-D) models more closely mimic native tissues. 3-D tissue models provide a means for systematic, repetitive and quantitative investigation of drugs, serving as platforms for screening of drugs as well as pharmacokinetic and pharmacodynamic analysis of drugs. That said, creating the more biologically relevant third dimension of tissue models requires a multidisciplinary approach and multidisciplinary expertise. Cambridge Healthtech Institute's Second Annual Engineering Functional 3-D Tissue Models meeting weaves together engineers, biologists and pharmacologists. As with any model, each specialty provides insights into the complete system advancing drug discovery and development, from designing the bioreactors, to engineering the 3-D models, to studying healthy versus diseased states, to utilizing drug screening assays.
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Monday, October 28
7:30 am Main Conference Registration and Morning Coffee
8:15 Chairperson's Opening Remarks
Jeffrey Morgan, Ph.D., Professor, Medical Science and Engineering and Co-Director, Center for Biomedical Engineering, Brown University
8:25 Integration of Systems Biology and Tissue Engineering in Drug Development
Linda G. Griffith, Ph.D., Professor, Biological Engineering and Mechanical Engineering and Director, Center for Gynepathology Research, Massachusetts Institute of Technology
Intense efforts in recent years to develop new therapies for chronic debilitating inflammatory diseases such as asthma, rheumatoid arthritis and inflammatory bowel disease have yielded many new promising classes of compounds, from kinase inhibitors, protease inhibitors and monoclonal antibodies directed at immune networks. Predicting efficacy (as well as off-target toxicities) in humans remains a significant challenge for therapies directed at these diseases, as intervention in a target node of a network may result in unintended compensation along other network paths or in off-target toxicities. To address these problems, systems biology approaches are being developed to predict phenotype, and responses to intervention, by linking extracellular communication networks to intracellular signaling networks using a compendium of data from patient samples, animal models and in vitro studies. Such approaches are being developed in parallel with a confluence of technologies to improve diagnostic tools and criteria, better classify patients according to clinical symptoms and findings and improve the information content of in vitro cell and tissue-based assays. This talk will focus on how to integrate systems biology approaches with 3-D in vitro models of liver and other organs.
9:05 Designing a Tunable 3-D Heterocellular Breast Cancer Tissue Test System
Karen J.L. Burg, Ph.D., Hunter Endowed Chair and Professor of Bioengineering, Director, Institute for Biological Interfaces of Engineering, Clemson University
The viability of a tissue-engineered product relies on cell-biomaterial interaction and the design of an appropriate 3-D microenvironment. This presentation will highlight examples showing the importance of microenvironment in influencing cellular behavior and will describe how one can purposefully tune this cell-material "handshake." The potential of specialized 3-D cellular systems in personalized medicine will be discussed.
9:45 Tissue Engineering in Magnetic Levitation 3-Dimensional Culture System
Mikhail Kolonin, Ph.D., Associate Professor, John S. Dunn Research Scholar, Jerold B. Katz Distinguished Professor in Stem Cell Research, The Brown Foundation Institute of Molecular Medicine Center for Stem Cell and Regenerative Medicine, University of Texas Health Science Center at Houston
We present an application of 3-D levitation tissue culture system based on magnetic nanoparticles to modeling white adipose tissue. We demonstrate efficient differentiation of mesenchymal progenitors into adipocytes achieved in parallel with endothelial cells organizing into vessel-like structures in 3-D organoids termed "adipospheres." This magnetic levitation approach, enabling the retention and self-organization of cell types composing a tissue in vivo, may provide advantages for quick and simple simulation of organs, cells of which are difficult to maintain in conventional culture systems.
10:15 Coffee Break
10:30 An Engineered Model of the Airways with All Primary Human Cells
Sonia Grego, Ph.D., Senior Scientist, Center for Materials and Electronic Technologies, RTI International
Microfluidic systems enable biomimetic cell cultures for more physiologically-relevant models of human organs such as the lung. The lung is a primary site of exposure to environmental insults and pathogens as well as an attractive drug delivery route. Microfluidic lung models often use immortal cell lines, which are conveniently maintained in culture but lack many of the morphological and functional characteristics of the original tissue. We have developed a biomimetic multicellular 3-D model of the human conducting airways including all primary lung cells. Primary cells are recognized as the closest in vitro representation of the tissue physiology. Our engineered cellular construct enables novel studies of therapeutics and viral infections.
11:00 Development of Engineered Trachea-Lung Constructs: The New Respiratory Models to Study Lung Development, Physiology, Pathology or Toxicology
Joan Nichols, Ph.D., Professor, Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch
Traditional cell culture assays to examine toxicity or pathogenicity in 2-D systems are flawed due to: 1) dependency on immortalized cell lines which do not adequately reflect biology and response of primary human cells, 2) reliance on single-cell systems that fail to recognize cell-cell interactions with the microenvironment and 3) reliance on artificial 2-dimensional monolayers for modeling complex diseases. Development of good in vitro human tissue models would help to bridge the gap in our current knowledge of lung responses, as well as provide a better understanding of lung development, physiology and pathology. A benefit of our current in vitro lung model is that hypotheses generated from review of data from human disease studies can be tested directly in engineered human tissue models. We are currently using complex 3-D models to examine cell-based responses, physiologic functions, pathologic changes related to development of lung disease and lung fibrosis.
11:30 Next-Generation Bioengineered 3-D Human Tissue-Equivalent Platform System to Validate High-Volume Vaccine Production
Thomas J. Goodwin, Ph.D., Disease Modeling and Tissue Analogues Laboratory, NASA
An advanced 3-D regenerative tissue-equivalent disease modeling and detection system for most major human organs has been developed using a NASA platform. Normal human cells, tissue-engineered to grow in bioreactors simulating aspects of microgravity, serve as a platform to identify progenitor cell and organoid cellular interactions, modulations in gene expression and cellular differentiation. This technology validates longitudinal DNA and RNA viral proliferation, genomics and host proteomic inflammatory responses. The human lung epithelial cell construct mimics human respiratory epithelium including polarization, tight junctions, desmosomes, microvilli, functional tissue markers and maintains a long-term viral infective state without loss of cellular function. This model is a paradigm shift for high-volume production of virus for vaccine production.
12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:30 Chairperson's Opening Remarks
Gregory Timp, Ph.D., Professor, Electrical Engineering and Biological Sciences, University of Notre Dame
1:35 3-D Intestinal Tissue Models
John March, Ph.D., Associate Professor, Biological and Environmental Engineering, Cornell University
Interactions between human upper intestinal cells and microorganisms populating the intestinal lumen are increasingly being resolved at the molecular level. We are developing in vitro tools to better understand how human epithelial cells develop in a 3-D environment and how bacteria and other organisms interact with these cells.
Anthony Bahinski, Ph.D., MBA, FAHA, Lead Senior Staff Scientist, Wyss Institute
Development of safe and effective drugs is currently hampered by the poor predictive power of existing preclinical animal models that often lead to failure of drug compounds late in their development. Given the tremendous cost of drug development and the long timelines involved, major pharmaceutical companies and government funding agencies are now beginning to recognize a crucial need for new technologies that can quickly and reliably predict drug safety and efficacy in humans in preclinical studies. Advances in bioengineering, material sciences, microfabrication and microfluidics technologies have enabled the development of microphysiological systems that mimic the functional units of an organ. These microsystems could potentially further our understanding of disease etiology and fill the critical need for improved model systems to predict efficacy, safety, bioavailability and toxicology outcomes for candidate compounds.
2:35 From iPSC to 3-D Skin Equivalents: Dynamic Platforms to Study Human Disease
Jonathan Garlick, D.D.S, Ph.D., Professor, Oral Pathology, School of Dental Medicine, Tufts University; Director, Center for Integrated Tissue Engineering and Professor, Tufts School of Medicine, School of Engineering and Sackler School of Graduate Biomedical Sciences
Induced pluripotent stem cells reprogrammed from somatic cells can now be developed into a broad spectrum of cell types. This technology provides important opportunities to use this replenishing source of stem cells to fabricate 3-D tissues. This presentation will describe how iPSC can be used to create 3-D, skin-like tissues that harbor the potential to improve drug screening and disease modeling. We will demonstrate how 3-D human tissues can be used to elucidate the function and screen the safety of iPSC-derived cells before their clinical use and how to best leverage 3-D tissue models to help advance "Disease in a Dish" to "Disease in a Tissue."
3:05 Refreshment Break in the Exhibit Hall with Poster Viewing
Customized 3-D Cell Cultures and Assays Showcase
All agree that 3-D cell models that are morphologically and functionally similar to native tissue hold the potential to improve in vitro cell-based assays. However, it is important to note that there is no one-size-fits-all solution; each cell type requires a different environment and different assays to screen them. This session showcases companies that are driving cell culture and screening assays into the new dimension of studying health vs. disease and drug response.
4:00 Tumor Microtissue Models to Study Gene Function Analysis
Jens M. Kelm, Ph.D., CSO & Co-founder, InSphero AG
Cancer cells in vivo are coordinately influenced by an interactive three-dimensional microenvironment. However, clinical relevant identification of drug targets and initial target validations are primarily done in two-dimensional cell culture systems resulting in high failure rates. The design of 3D co-culture models which reflect better heterotypic cell interactions enables investigations on the phenotypic impact of gene function with a model that more closely resembles tumor growth in vivo.
4:20 Automation, A New Dimension in 3D Cell Based Screening
Susanne Braum, Ph.D., Senior Market Manager, Applications & Solutions, Tecan
The adoption of 3D cell cultures for cell based screening has improved assay results significantly. Routine implementation of automation using liquid handling robotics and detection devices is mandatory to achieve highest reliability and consistency. Tecan is showing solutions of automated 3D technologies on its Freedom EVO® liquid handling robotic system with its microplate readers and uses optimized read out technologies to automatically assess 3D cell based structures.
4:40 Novel 3D Cell Migration Assay for Drug Efficacy and Cytotoxicity Testing Using an iPod
Glauco R. Souza, Ph.D., CSO, Nano3D Biosciences, Inc.
We will introduce a label-free cell based assay which combines 3D cell culturing by magnetic levitation and cell migration to quantitatively evaluate drug efficacy and toxicity using an iPod Touch. Results obtained with this high-content assay are significantly faster (6h to 5 days) than traditional 3D assays which rely on cell proliferation (10 to 30 days). We will present results with primary cells and cell lines that show significant differences in IC50 between 3D and 2D with various compounds: doxorubicin, ibuprofen, retinoic acid, and SDS.
5:00 Welcome Reception in the Exhibit Hall with Poster Viewing
6:00-9:00 Dinner Short Course*
SC2: Automating a 3-D Culture Screening Laboratory: Meeting the Challenges
Stephen Gundry, Research Scientist, Electrical Engineering, The City College of New York, CUNY
Nicolas Atrux-Tallau, Ph.D., Research Scientist, École Supérieure de Physique et de Chimie Industrielles ParisTech
Markus Rimann, Ph.D., Research Associate, Life Sciences and Facility Management, Zurich University of Applied Sciences
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*Separate registration required
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