3D Cellular Models
Cell and 3D models that capture both the organization and multicellular complexity of the target provide the most powerful tool for screening the effects of therapeutic candidates and studying disease progression. As with any 3D model, weaving together tissue engineers who are developing the 3D tissue models with biologists who are studying healthy vs. diseased states and pharmacologists who are utilizing high-throughput screening assays provides insight into the complete system.
TUESDAY, AUGUST 12
7:30 Breakfast Technology Workshop (Sponsorship Available)
DISEASE PROGRESSION
8:30 Chairperson’s Remarks
Melvin Schindler, Ph.D., President, NanoCulture, LLC
8:35 3D Cell Culture Models for the Study of Normal and Malignant Mammary Epithelial Cells
Britta Weigelt, Ph.D., Post-Doc, Mina J. Bissell Laboratory, Life Sciences Division Lawrence Berkeley National Laboratory
The normal mammary gland and invasive breast tumors are composed of multiple cell types and extracellular matrix in three-dimensional (3D) space. The in vitro study of normal and malignant mammary epithelial cells as two-dimensional monolayers results in the loss of structure and tissue function. In contrast, 3D culture systems allow cells to organize into structures that mimic their in vivo architecture. Such 3D cell culture models have great potential for the investigation of gene functions, signaling pathways as well as drug testing and target validation in a physiologically relevant context.
9:05 Polymeric Systems for Tumor Engineering
Claudia Fischbach-Teschl, Ph.D., Assistant Professor, Department of Biomedical Engineering, Cornell University
Three-dimensional micro-environmental conditions play a fundamental role in tumorigenesis, but 2-D culture approaches fail to mimic these conditions in vitro. Polymeric scaffolds provide powerful tools to engineer 3-D cancer models that overcome these limitations by recapitulating typical tumor-micro-environmental characteristics in vitro. Cancer cells exposed to these biomimetic culture conditions exhibit increased angiogenic capacity, promote tumor growth in vivo, and are less sensitive to chemotherapy. Consequently, engineered 3-D tumor models may be invaluable for basic research of cancer and drug testing under pathologically more relevant conditions.
9:35 A 3D Model to Study Neurodegenerative Disorders of the Spinal Cord in Vitro
François Berthod, Ph.D., Assistant Professor, Department of Surgery, Laval University
To study motor neurons in a physiological environment, we developed a three-dimensional tissue-engineered in vitro model allowing the analysis of the axonal migration and myelination of motor neurons combined with Schwann cells. In this model, myelination of motor axons was demonstrated for the first time in vitro.
10:05 Technology Spotlight
Liver3 and Skin3 3D Tissue Cultures for ADMET and Efficacy Assessment of Drug Candidates, Chemicals and Cosmetics
Dawn R. Applegate, Ph.D., President & CEO, RegeneMed
RegeneMed’s 3-D human and animal tissue cultures in multiwell plates provide physiologically relevant replacements to current industry-standard animal and cell-based tests that have limited human chemical and drug toxicity prediction. Liver3 and Skin3, 3-D liver and cultures, sustain tissue function for months, providing off-the-shelf available, reproducible, reusable, species-specific prediction of ADMET and efficacy measures for new drug candidates, chemical entities and consumer products. The long-term tissue-specific function enables in vitro assessment of previously unattainable endpoints such as bioavailability, drug-drug interactions, and chronic toxicity. Services include animal dosing and monolayer culturing of sibling cells for comparison to 3-D tissue cultures, contract testing services, and other 3-D tissue types.
10:20 Networking Coffee Break, Poster and Exhibit Viewing
SCREENING
11:00 Microscale 3D Models of the Liver
Linda Griffith, Ph.D., Professor of Teaching Innovation, Biological Engineering, MIT
11:30 Development of a 3-D Model System Using Human Mesenchymal Stem Cells in a Modular Perfusion Bioreactor System
Teng Ma, Ph.D., Associate Professor, Department of Chemical and Biomedical Engineering, Florida State University
Three-dimensional (3-D) culture systems possess fundamental advantages over traditional techniques for providing insight into the native characteristics of cells, and are powerful tools for tissue-engineering and drug screening applications. We have developed a 3-D model system using porous poly(ethylene terephthalate) (PET) scaffolds and human mesenchymal stem cells (hMSCs) and investigated 3-D construct development under various oxygen tensions and flow conditions in a perfusion bioreactor system. Human MSCs are an ideal model system owing to their extensive developmental potentials of proliferation and multi-lineage differentiation, whereas the non-degradable, highly porous 3-D PET scaffolds provide long-term, stable structural support for 3-D cellular construct development. The modular perfusion bioreactor allows the generation of various flow regimens that can be tailored to meet the requirements at various construct developmental stages. Taken together, the 3-D model system developed in our lab has the capacity to control the innate tissue development process and has significant potential for tissue regeneration and for screening therapeutic candidates.
12:00 pm Engineered Heart Tissue Based High-Throughput Phenotyping and Toxicity Testing for Drug Discovery
Tetsuro Wakatsuki, Ph.D., Co-Founder and Chief Scientist, InvivoSciences LLC; Assistant Professor, Medical College of Wisconsin
InvivoSciences LLC developed a high-throughput biological phenotyping system by which the scientists can assess various physiological parameters of cardiac tissues using engineered heart tissues (EHTs). The physiological measurements include EHT™ contractile activities and metabolic states. To validate use of EHT based high-throughput phenotyping, the system succeeded to detect well-characterized differences in susceptibility of myocardium to a hypoxic stress among inbred rat strains. The application of EHT system in detecting compound toxicity including arrhythmic potency will be discussed. We will also clarify the limitations of an engineered tissue based approach as well as their great advantages.
12:30 Luncheon Technology Workshop (Sponsorship Available) or Lunch on Your Own
1:45 Session Break
CASE CONSIDERATIONS FROM PHARMA
2:00 Chairperson’s Remarks
Jonathan Garlick, Ph.D., DDS, Professor, Division of Cancer Biology and Tissue Engineering, Tufts University
2:15 Case Study One
Use of Three Dimensional Tissue Culture Models of Human Skin as an Early Safety Assessment of Integrin Blocking Antibodies
Heather Adkins Huet, Ph.D., Tumor Cell Growth and Adhesion, Biogen Idec
The use of 3D tissue technology is going to have a growing impact on drug discovery and validation for the determination of efficacy and early reads on safety. In the oncology setting, we are seeing a greater number of targeted therapies directed to proteins that play a role in the tumor microenvironment, so understanding the behavior of our drugs in complex biological systems is information that can not be garnered from traditional cell culture models. We have taken advantage of 3D models of human skin to understand if antibodies directed to the integrin α6β4 can penetrate the complex architecture of the skin and/or affect wound closure, giving us an early indication of potential safety concerns from our inhibitors and potential mechanisms to investigate in future toxicology studies.
2:35 Case Study Two
Skin Equivalents in Technology Development
Deborah Finlay, Ph.D., Senior Scientist, Global Biotechnology Division, Procter & Gamble Company
P&G has a long history of supporting efforts to develop in vitro models that predict human skin responses, for safety assessments and technology qualification. As an outcome of this work, human skin equivalents are being used successfully to evaluate the skin compatibility of cosmetic technologies and formulations. In addition, these in vitro models are proving useful in qualifying new skin care technologies and their cosmetic modes of action. We continue to integrate new in vitro methods into safety and technology identification efforts as these methods are developed and validated, looking for improvements that strengthen our ability to predict human skin responses. Toward this end, we anticipate the future will realize the integration of organotypic cultures that more appropriately model human skin types and conditions than available currently, and improve the flow of technology discovery from the identification of targets through to pre-clinical testing.
2:55 Networking Refreshment Break, Poster and Exhibit Viewing
CELLS AS TOOLS
3:30 Microgengineered Hydorgels for Tissue Engineering
Ali Khademhosseini, Ph.D., Assistant Professor, Harvard-MIT Division of Health Sciences and Technology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School
Hydrogel biomaterials have been extensively used in various tissue engineering applications since they provide the cells with a hydrated 3D microenvironment that mimics the native extracellular matrix. More recently, the ability to engineer the size and shape of biologically relevant hydrogels has generated new opportunities in addressing challenges in tissue engineering such as vascularization, tissue architecture and cell seeding limitations. Presented will be the work from our group regarding the engineering of microscale hydrogels with controlled features and their applications to tissue engineering using a ‘bottom-up’ and a ‘top-down’ approach. Top-down approaches can be used to directly engineer the microvasculature into cell laden hydrogels. Also, the ability to engineer functional tissue building blocks can be used to generate a scalable approach in which smaller units can be assembled to generate larger tissues with desired function and architecture.
4:00 Programming Cells in Situ
David Mooney, Ph.D., Gordon McKay Professor, Bioengineering, Harvard University
There are hundreds of clinical trials of cell therapy currently underway, with the goal of curing a variety of diseases, but simple cell infusions lead to large-scale cell death and little control over cell fate. We propose a new approach, in which material systems are first used either as cell carriers or attractors of host cell populations, and in either case the material then programs the cells in vivo and ultimately disperses the cells to surrounding host tissues or organs to participate in tissue regeneration or destruction.
4:30 3D in Vitro Models for Breast and Prostate Cancer
David L. Kaplan, Ph.D., Professor, Biomedical Engineering, Tufts University
5:00 Panel of Experts Discussion
What Makes 3D Systems More in Vivo Like?
Moderator: Jonathan Garlick
Panelists: Dawn Applegate, Linda Griffith, David Kaplan, Melvin Schindler, Claudia Fischbach-Teschl
Back by Popular Demand!
5:30 Solutions @ CELLutions – Break-out Discussion Groups
Time has been designated for facilitated discussion groups with specific themes. This unique opportunity allows conference participants to focus on a topic and exchange ideas, information, experiences, and develop future collaborations.
6:30 Close of Day