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3D Cell Culture: Organoid, Spheroid, and Organ-on-a-Chip Models

Physiologically relevant complex cellular models that are predictive of human response are needed to improve drug discovery and toxicity testing in order to reduce costly late-stage attrition. 3D cell models have the ability to create tissue-specific structure and function, allowing more predictive in vitro assays. Cambridge Healthtech Institute’s Inaugural 3D Cell Culture meeting will cover the latest advances in tissue engineering and assay development for organoid, spheroid, and organ-on-a-chip models, including their applications in efficacy and safety screening, functional analysis, and compound de-risking. Coverage will include primary and stem cell models, complex co-culture cell models, tumor spheroid models, novel organ-on-a-chip models, and more.

Day 1 | Day 2 | Short CoursesDownload Brochure

Sunday, November 8

5:00 pm Short Course Registration and Main Conference Pre-Registration

6:00-9:00 (SC1) Dinner Short Course*: Introduction to High-Content Phenotypic Screening

*Separate registration required.

Monday, November 9

7:00 am Conference Registration and Morning Coffee

Organoids and Primary Organotypic 3D Culture in Drug Discovery

8:00 Chairperson’s Opening Remarks

David Grainger, Ph.D., Distinguished Professor, Pharmaceutical Chemistry, University of Utah

8:10 Characterizing Organotypic Tumor Tissue Slice Culture for Use in Drug Discovery

Emma Davies, Ph.D., Senior Scientist, Oncology iMed, AstraZeneca

Preclinical in vitro models that better represent the complexity of an in situ human tumor are being sought as part of the IMI project PREDECT (www.predect.eu). It is hoped that better recapitulation of the clinical situation, preclinically, will greatly improve target validation and ultimately get better drugs to patients. As part of PREDECT we have been investigating the use of organotypic slice culture for cultivation of tumor material ex vivo.

8:35 High-Throughput Screening Using a Primary Human 3D Organotypic Culture

Hilary Kenny, Ph.D., Research Associate (Assistant Professor), Obstetrics & Gynecology, University of Chicago

The tumor microenvironment contributes to cancer progression, metastasis and drug resistance. A multilayered culture containing primary human fibroblasts, mesothelial cells and extracellular matrix was adapted into a robust and reliable 384- and 1,536-multi-well high-throughput screening assay that reproduces the human ovarian cancer metastatic microenvironment. The identified inhibitors were validated using multiple cells and independent in vitro and in vivo secondary assays. These assays specifically investigated the effect of the compounds on ovarian cancer cell adhesion, invasion, proliferation and metastasis to the peritoneal microenvironment. Collectively, these findings show that a 3D organotypic culture can be adapted for high-throughput screening.

9:00 Analyses of Prostate and Bladder Tumor Organoids

Michael M. Shen, Ph.D., Professor, Medicine and Genetics and Development, Columbia University

9:25 A 3D Culture Model of Alzheimer’s Disease: Challenges and Perspectives

Doo Yeon Kim, Ph.D., Assistant Professor, Neurology, Genetics and Aging Research Unit, Massachusetts General Hospital, Harvard Medical School

We recently developed a human neural cell culture model of Alzheimer’s disease (AD) based on a three-dimensional (3D) cell culture system. This unique cellular AD model recapitulated key events of the pathogenic cascade of this disease, including β-amyloid plaques and neurofibrillary tangles. In this talk, I will present recent updates on our 3D culture model and discuss challenges and prospects.

9:50 Sponsored Presentation (Opportunity Available)

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

10:50 3D Brain Models to Study Neurotoxicity and Neurodegeneration

Lena Smirnova, Ph.D., Research Associate, Johns Hopkins Center for Alternatives to Animal Testing, Johns Hopkins University Bloomberg School of Public Health

The increasing incidence of neurodevelopmental disorders and lack of cure for neurodegenerative diseases such as Parkinson’s require new human-relevant models. iPSCs allow addressing gene-environment interactions. Therefore, we developed two 3D human neuronal models: (1) human iPSC-derived 3D mini-brains to recapitulate neurodevelopment and after maturation to selectively damage dopaminergic neurons by Parkinson agents, and (2) a homogeneous LUHMES 3D dopaminergic neuronal model, to study their molecular signatures and pathways.

11:15 In vitro Hydrogel-Based Culture of Patient-Derived Xenografts for Cancer Studies

Daniel A. Harrington, Ph.D., Assistant Director, Collaborative Research Laboratory; Faculty Fellow, BioSciences, Rice University

Many primary cell types, including PDX models, are not readily grown on conventional 2D tissue culture substrates. We describe our ongoing efforts using customizable, biocompatible hydrogels to enable the extended laboratory culture of cancer PDXs and other primary cells in 3D. This platform permits the use of these desirable cell lines for laboratory manipulation and drug testing in miniaturizable formats.

11:40 Addressing Challenges in Organoid Culture Using a High-Throughput Microraft Array Platform

Adam D. Gracz, Ph.D., Postdoctoral Fellow, Magness Lab, Gastroenterology and Hepatology, University of North Carolina, Chapel Hill

Organoid cultures have emerged as a powerful tool for understanding adult stem cell biology in a wide range of tissues. However, conventional organoid methodology presents unique challenges in terms of accurate quantification and retrieval of samples. Bioengineered microraft arrays address these challenges by providing a high-throughput platform for long-term clonal tracking and retrieval of organoids. As proof of concept, we use microraft arrays to study stem cell-niche interaction and probe the molecular characteristics of organoid phenotypes.

12:05 pm Comparing 2D Kidney Cell and 3D Kidney Organoid Cultures for in vitro Drug Toxicity Assays

David Grainger, Ph.D., Distinguished Professor, Pharmaceutical Chemistry, University of Utah

Many new 3-D cell culture models seek to preserve in vivo-like organization within tissue-like or organoid constructs to elicit more relevant pharmacological toxicity and toxicity marker up-regulation. We report our development of a kidney proximal tubule (PT) 3D gel-based organoid culture comparison against conventional 2D kidney cell cultures to assess nephrotoxicity markers from common model drugs and select nanoparticles.

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

Engineering Functional Organ-on-a-Chip Models

2:00 Chairperson’s Remarks

Dan Dongeun Huh, Ph.D., Wilf Family Term Chair & Assistant Professor, Bioengineering, University of Pennsylvania

2:05 Microengineered Physiological Bio-Mimicry: Human Organs-on-Chips

Dan Dongeun Huh, Ph.D., Wilf Family Term Chair & Assistant Professor, Bioengineering, University of Pennsylvania

This talk will present interdisciplinary research efforts focused on leveraging unique capabilities of microfluidics and microfabrication to develop microengineered biomimetic models that reconstitute complex structures, dynamic microenvironments, and physiological functionality of human organs. Specifically, I will talk about: i) a bioinspired microsystem that mimics the structural and functional complexity of the alveolar-capillary interface in the living human lung, ii) a specialized in vitro human disease model that simulates pulmonary edema, and iii) a microengineered model of the ocular surface in the human eye.

2:30 Replicating Organ and Tissue Function Using Microfabrication

Joseph L. Charest, Ph.D., Group Leader, Biomedical Microsystems, Charles Stark Draper Laboratory, Inc.

Microfabricated systems can mimic components of native tissue resulting in realistic in vitro models. Specifically, micro/nano-topography, microfluidically-controlled fluid flow, and small scale structures can guide cells to form tissue with organ- or tissue-specific function. The microfabrication approach yields models representing kidney and tumor as well as other tissues, with the potential to include unique features and new metrics to evaluate and predict efficacy of new therapies.

2:55 3D Cell Culture for Quantitatively Identifying Form and Function of Cancer Stem Cells

Muhammad H. Zaman, Ph.D., Professor, Howard Hughes Medical Institute; Professor, Biomedical Engineering and International Health, Boston University

Understanding how cells respond to mechanical, chemical and structural cues in 3D environments is not only important from a fundamental perspective, but also needed for designing better therapeutics. Our work, combining multi-scale simulations, novel biomechanical tools and biomimetic hydrogels will analyze cancer cell response to chemotherapeutics, and optimization of 3D culture to analyze cellular form and function during various stages of disease.

3:20 Microstructured Environments for Epithelial to Mesenchymal Transition (EMT) Assays and Drug Discovery

Daniel Irimia, M.D., Ph.D., Assistant Professor, Surgery, Massachusetts General Hospital, Harvard Medical School, Shriners Burns Hospital

Current assays for cancer cell migration are a compromise between throughput, detailed characterization, and relevance to human condition. Designed to overcome these limitations, novel microfluidic devices provide 3D microstructured environments for the study of cancer cell migration. Inside these devices, EMT-activated cancer cells advance through micropillar arrays as a collective front that scatters individual cells, resembling the phenotype of malignant cells that invade the tissues surrounding tumors. The predictable trajectories of the moving cells allow precise measurements of migration parameters, enable higher throughput studies of EMT, facilitate chemosensitivity quantification, and serve as a discovery tool for the mechanisms driving cancer cell invasion.

3:50 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 3D Printed and Nanofabricated Scaffolds for Engineering Contractile Cardiac Muscle

Adam Feinberg, Ph.D., Associate Professor, Materials Science & Biomedical Engineering, Carnegie Mellon University

We are developing tissue engineering technologies to build the extracellular matrix (ECM) from the bottom-up just like cells do during embryogenesis and wound healing. To do this, we have developed a biomimetic, surface-initiated assembly process that recapitulates how cells naturally build the ECM in tissues at the nanoscale as well as 3D bioprinting techniques to create larger structures that incorporate more intricate anatomy. Together, these approaches provide a reductionist system where complexity can be engineered back into the matrix system, which we are exploiting as a 3D cardiac tissue engineering platform and basic science tool.

5:10 Heart-on-a-Chip Platforms for Drug Toxicity Testing

Ville Kujala, Ph.D., Postdoctoral Fellow, Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University

The Disease Biophysics Group at Harvard University has developed heart-on-a-chip platforms for cardiac contractility and electrophysiology measurements. Here, we will cover the latest advancements and their applications in drug toxicity testing.

5:35 Organs-on-a-Chip for High-Content Drug Screening

Kevin E. Healy, Ph.D., Professor, Bioengineering, University of California Berkeley

Drug discovery and development are hampered by high failure rates attributed to reliance on non-human animal models employed during safety and efficacy testing. With the discovery of patient-specific human induced pluripotent stem (iPS) cells, we can now develop in vitro disease specific tissue models to be used for high-content drug screening and patient specific medicine. This presentation will discuss our progress in developing integrated in vitro models of human cardiac and liver tissue based on populations of normal and patient specific hiPS cells differentiated into cardiomyocytes or hepatocytes, respectively. Our in vitro integrated physiological system has the potential to significantly reduce both the cost and duration of bringing a new drug candidate to market.

6:00-7:00 Welcome Reception in the Exhibit Hall with Poster Viewing

6:45 Short Course Registration

7:00-9:00 (SC2) Dinner Short Course*: Screening Strategies for Cancer Immunotherapy

*Separate registration required.

Day 1 | Day 2 | Short Courses | Download Brochure

Tuesday, November 10

7:00 am Conference Registration and Morning Coffee

3D Spheroid Models for Drug Screening

8:00 Chairperson’s Opening Remarks

Jeffrey Morgan, Ph.D., Professor, Medical Science & Engineering, Brown University

8:10 Designer 3D Spheroids for Testing Drugs and Drug Uptake

Jeffrey Morgan, Ph.D., Professor, Medical Science & Engineering, Brown University

This talk will focus on the use of our micro-mold technology to form designer 3D spheroids of mixed cell types. We are quantifying drug transport and drug elimination and the role of efflux pumps.

8:35 Drug Response in the Context of the 3D Tumor Microenvironment

Eugen Dhimolea, Ph.D., Instructor, Medicine, Dana-Farber Cancer Institute, Harvard Medical School

In vitro 3D cultures of malignant cell lines and patient-derived samples mimic the architecture and pathophysiology of human tumors more faithfully than conventional 2D cultures. In addition, 3D cultures often reassume the molecular profile and drug-resistant phenotype observed in the clinic. The development of appropriate tissue-engineered tumor models and their adaptation for scalable drug testing will contribute significantly to understanding cancer biology, discovering new therapeutics and designing personalized cancer treatments.

9:00 3D Spheroids for Anti-Cancer Drug Screening

Darren Finlay, Ph.D., Research Assistant Professor, Sanford-Burnham-Prebys Medical Discovery Institute

3D spheroid cultures better recapitulate true tumor architecture and nutrient gradients than do traditional 2D monolayers. Here we demonstrate how 3D cancer spheroids show differential sensitivity to relevant anti-cancer agents and how co-culture with various stromal, or non-tumor, factors can greatly modulate chemosensitivity. Furthermore, we show how patient tumor-derived 3D spheroid samples can be used for precision medicine profiling.

9:25 Tumor Model Systems Recreating Aspects of the Tumor Microenvironment for Understanding Multimodal and Novel Cancer Nanotherapies

Meenakshi Upreti, Ph.D., Assistant Professor, Pharmaceutical Sciences, University of Kentucky

9:55 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Reaching Physiological Relevance with 3D Cell Culture

Sophie A. Lelièvre, D.V.M., LLMPH, Ph.D., Professor, Basic Medical Sciences & Cancer Pharmacology; Director, 3D Cell Culture Core Facility (3D3C) in Discovery Park, Purdue University

Relevance to physiological parameters of real tissues is a requirement for any 3D cell culture model to bring useful information and findings. Using the example of the mammary gland, I will discuss the criteria that inform the choice of the 3D culture system, including spheroid-like culture, cultures favoring the interaction of different tissues, and organ-on-a-chip culture in order to provide a reproducible model for basic and translational research.

11:10 High-Throughput 3-D Small Cell Number Spheroids for Ovarian Cancer Drug Screening for Individualized Therapies

Geeta Mehta, Ph.D., Assistant Research Scientist, Biomedical Engineering, University of Michigan

We have recently established a high-throughput platform for stable formation of uniform-sized ovarian cancer spheroids using very low cell numbers (ranging from 10 cells to 100 cells). We assess the utility of spheroids generated in this platform by performing a chemosensitivity assay. We believe that this platform can be applied to the use of rare cancer stem-like cell populations found in primary patient samples and ascites. The stable incorporation of low cell numbers ensures that these samples can be handled prudently in order to study novel and emerging drugs that target rare cancer initiating cells and chemoresistant populations.

11:35 Developing Spheroid Preclinical Models of Advanced Prostate Cancer for High-Throughput Screens

Donna Peehl, Ph.D., Research Professor, Urology, Stanford University

Prostate cancer (PCa) is under-represented in large cell line panels used to screen drugs, and the most predictive preclinical model of 3D culture has never been widely applied to screen PCa cells. New methodologies to culture spheroids from patient tissues and xenografts will provide models that encompass the genetic heterogeneity of advanced PCa, and facilitate high-throughput assays to identify new therapeutic leads and correlate drug response with genetic phenotype.

12:00 pm 3D in vitro Modeling of Epithelial Ovarian Cancer for Biomarker Discovery

Simon A. Gayther, Ph.D., Professor, Preventive Medicine, University of Southern California Keck School of Medicine

We have established multiple ovarian cancer cell lines and normal ovarian epithelial cells as 3D multicellular spheroid models following cell culture using polyHEMA-coated tissue culture plastics. 3D EOC cell cultures display many of the histological features of primary tumors not present in 2D monolayer cultures. Complex cell/cell and cell/matrix adhesions can be seen throughout the surface of the cell membrane of each cell. Cells within spheroids typically cycle more slowly, and upregulate expression of tumor-associated proteins that are highly expressed in primary ovarian cancer specimens. We have also shown that the 3D models are typically more resistant to chemotherapeutic agents and small molecule therapies than 2D models.

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:10 Close of Conference

Day 1 | Day 2Short CoursesDownload Brochure

For questions about the meeting, please contact:
Julia Boguslavsky
Executive Director, Conferences (CHI)
Cambridge Healthtech Institute
E-mail: juliab@healthtech.com

For sponsorship and exhibit sales information, please contact:
Katelin Fitzgerald
Senior Business Development Manager
Cambridge Healthtech Institute (CHI)
Phone: (+1) 781-972-5458
Email: kfitzgerald@healthtech.com 

For media and association partnerships, please contact:
Jaime Hodges
Marketing Manager
Cambridge Healthtech Institute (CHI)
Phone (+1) 781-972-5429
Email: jhodges@healhtech.com