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2013 Archived Content

Screening and Functional Analysis of 3-D Models Header

While more informative than cell-free biochemical assays, monolayer or suspension cell culture HTS assays still fail to accurately reflect the human cellular microenvironment. There is a need for physiologically-relevant cellular models for drug screening and functional analysis that provide high predictive value for clinical efficacy and safety of compounds. The three-dimensional cell culture models mimic the human tissue microenvironment and provide more accurate information for compound and target selection, thereby reducing late-stage attrition. Cambridge Healthtech Institute’s Inaugural Screening and Functional Analysis of 3-D Models meeting will explore the use of 3-D models to profile compound action and predict toxicity and efficacy. The meeting will cover assay development using 3-D cellular models, high-content analysis and imaging of 3-D models, and applications of screening 3-D models for compound profiling and target discovery/validation.


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Tuesday, October 29

12:00 pm Main Conference Registration

 

Compound Characterization with 3-D Models 

1:30 Chairperson’s Opening Remarks

1:35 Application of Clonogenic 3-D Assays in High-Throughput Screening and Compound Optimization/Characterization

Aaron MorrisAaron Morris, Ph.D., Lab Head, Cancer Biology, Sanofi Oncology

The ability to grow in an anchorage-independent manner is a hallmark of cancer cells. A 3-dimensional clonogenic growth assay in soft agar leverages this phenotype for assessment of cancer-signaling dependencies. We have performed a 3-D multi-cell line parallel phenotypic high-throughput screen with our proprietary compound collection to identify pathways, targets and chemical matter with selective anti-tumor activity. This 3-D soft agar assay has been further optimized to support hit-to-lead optimization efforts and a full range of MoA characterization studies.

2:00 High-Throughput 3-D Cell Culture for Drug Discovery and Human Toxicology

Jonathan Dordick, Ph.D., Isermann Professor of Chemical and Biological Engineering, and Vice President for Research, Rensselaer Polytechnic Institute

The need for increased knowledge of drug candidates at early stages of discovery is driving the development of new, high-throughput, and high-content technologies. The centerpiece of our approach involves the use of a miniaturized three-dimensional mammalian cell culture platform that consists of 500-1,000 individual cell cultures on a microscope-size slide “biochip.” A broad range of human and animal cells have been used on the chip platform, including primary cells and transformed cell lines from multiple tissues, as well as human and animal stem cells. Furthermore, many assays that are traditionally performed in well plates can be adapted to the high-throughput 3-D cell culture chip.

2:25 Development Challenges with 3-D Tumor Spheroid Culture and Endpoint Measurements Relevant to Drug Screening

Martina Fitzek, Associate Principal Scientist, Discovery Sciences, AstraZeneca

The pharmaceutical industry faces increasing pressure to deliver novel differentiated products to fulfill unmet medical needs. We have seen a trend towards increased interest in the use of physiologically-relevant systems applied to drug screening campaigns. Emerging techniques in the 3-D culture area can position cells in an environment which offers the potential for measuring more relevant functional responses. We will describe our experience using different techniques to generate tumor cell-derived spheroids and the methods we have applied to measure their properties. The presentation will be an assessment of the potential benefits and the challenges that need to be overcome to successfully exploit the more physiologically-relevant properties of tumor spheroids and implications for future drug screening.

2:50 Sponsored Presentations (Opportunities Available. Contact Ilana Quigley at 781-972-5457 or iquigley@healthtech.com.)

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing

 

High-Content Analysis of 3-D Models 

4:15 Development of a Novel Reversible Cell Scaffold (RCS) System for Use with High-Content Imaging Platforms

Anthony M. Davies, Ph.D., Director, Irish National Center for High-Content Screening and Analysis (INCHSA)

In this presentation we will for the first time showcase a completely novel system of cell culture permitting cells to be first grown in 3-D and then harvested as required. This system has been specifically designed for use with HCS/A imaging platforms, automated liquid handling and HTS. Unlike any other 3-D assay systems currently used, our technology does not rely upon solid gel matrices, scaffolds, micro-patterned surfaces or hanging drop assay systems to achieve reproducible cancer spheroid growth. Indeed many of the inherent technical issues surrounding these technologies are avoided by utilizing this novel 3-D culture technology. This reversible cell scaffold system comprises of two individual components: (i) a low-viscosity liquid support/scaffold; and (ii) an agent that deactivates the scaffold, permitting sedimentation of cellular structures under gravity, permitting either high-content imaging in situ or recovery for further analysis such as gene expression or biochemical analysis. This system of suspension/deactivation has been used to great effect in both high-content imaging and subsequent gene expression studies.

4:40 3-D Models of Metastatic Cancer Targeting Tumor-Initiating Cells via High-Content Analysis

Daniel V. LaBarbera, Ph.D., Assistant Professor, Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado

In vitro 3-D models, particularly multicellular tumor spheroids (MCTS), offer a systems biology approach to bridge information from molecular target and 2-D cell-based screening, with in vivo models, to improve the predictability of drug discovery. We will discuss our current research with 3-D models using fluorescent reporter models, suitable for high-content imaging drug discovery. Specifically, we will describe methods to measure local (single-cell) and global (entire MCTS) changes after small molecule treatment targeting drug resistant invasive phenotypes of cancer.

5:05 Presentation to be Announced

 

6:00-9:00 Dinner Expert ThinkTank*

SC4: How to Meet the Need for Physiologically-Relevant Assays?

Moderator: Lisa Minor, Ph.D., President, In Vitro Strategies, LLC

Panelists:

Anne Bang, Ph.D., Director, Cell Biology, Sanford-Burnham Medical Research Institute

Anthony M. Davies, Ph.D., Director, Irish National Center for High-Content Screening and Analysis (INCHSA)

Marina Fitzek, Associate Principal Scientist, Discovery Sciences, AstraZeneca

 

Aaron MorrisAaron Morris, Ph.D., Lab Head, Cancer Biology, Sanofi Oncology

 

 

 

 

 

 

Michelle Palmer, Ph.D., Director, Discovery and Preclinical Research, Broad Institute

Caroline Shamu, Ph.D., Lecturer, Systems Biology and Director, ICCB-Longwood, Harvard Medical School

 

Dr TaylorD. Lansing Taylor, Ph.D., Director, University of Pittsburgh Drug Discovery Institute and Allegheny Foundation; Professor, Computational and Systems Biology, University of Pittsburgh

 

 

» View Details 

*Separate registration required 

 


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Tissue Engineering and
3-D Models: Past and Future