Cambridge Healthtech Institute’s 5th Annual

3D Cellular Models

Engineering Predictive Preclinical Screening Models

June 18-19, 2019


Inadequate representation of the human tissue environment during a preclinical screen can result in inaccurate predictions of a drug candidate’s 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 5th Annual 3D Cellular Models conference as they discuss strategies that accelerate the identification of novel therapeutic leads.

Final Agenda

Tuesday, June 18

7:00 am Registration Open and Morning Coffee

MODELING DISEASES TO IDENTIFY NOVEL THERAPIES

8:00 Chairperson’s Remarks

Remko van Vught, Director, Business Development, Mimetas B.V.


8:10 KEYNOTE PRESENTATION: Human Organs on Chips for Drug Discovery and Development

Rachelle Prantil-Baun, PhD, Senior Staff Scientist, Wyss Institute

We have applied this technology towards understanding mechanisms of infectious disease, inflammation, and cancer. Additionally, this microfluidic culture technology provides better predictive models for drug efficacy and toxicity. Recently, we have created a ‘Human Body-On-Chips’ platform to address limitations of drug development where animal models do not predict drug pharmacokinetic and pharmacodynamics (PK/PD) in human clinical trials.

8:40 Adult Stem Cell Organoids: A Patient in the Lab

Robert Vries, PhD, CEO, Hubrecht Organoid Technology (HUB)

Key to the development of the HUB Organoid Technology was the discovery of adult stem cells by Hans Clevers. Provided with the appropriate growth factors, the adult stem cells form a polarized epithelium in which stem cells, and their differentiated offspring, maintain their natural hierarchy and function. In addition, the organoids are genetically stable during prolonged culture. Subsequently, we developed Organoid technology for most other epithelia. High establishment efficiency means that we can use the Organoid Technology to generate disease models from virtually all patients.

9:10 Contracting Human Muscle Models in a Dish for Physiological Drug Screening

Keller_HansjoergHansjoerg Keller, PhD, Senior Investigator I, Musculoskeletal, Novartis Institutes for BioMedical Research

There is a high need for in vitro human microphysiological assay systems in order to enhance the translatability of preclinical drug discovery and development efforts. Using a 3D bioprinting approach, we have developed a new screening platform for the automated fabrication of functional human skeletal muscle tissue models attached between two posts in microwells, which can be electrically stimulated. It is a promising new in vitro exercise model to identify drugs regulating muscle force and fatigue.

9:40 Grand Opening and Coffee Break in the Exhibit Hall with Poster Viewing

ENGINEERING 3D BBB MODELS

10:25 Blood-Brain-Barrier Organoids for Modeling the Permeability of CNS Therapeutics

Cho,_Choi_FongChoi-Fong Cho, PhD, Instructor, Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School

The inability of most systemically delivered therapeutics to cross the blood-brain-barrier (BBB) is considered a major barrier to effective treatment for various neuropathologies. Techniques to model the BBB in vitro are crucial tools to help predict brain uptake of drug candidates prior to in vivo studies. We describe here the utility of 3D multicellular BBB organoids made of human brain endothelial cells (ECs), pericytes and astrocytes as a screening tool for brain-penetrating agents.

10:55 3D Models of the Blood Brain Barrier

Marsh_GrahamGraham Marsh, PhD, Scientist, Biogen

The Blood-Brain-Barrier (BBB) is a very tightly regulated interface that limits the passage of molecules from the blood stream into the brain. BBB permeability is a critical parameter to evaluate when screening potential therapies. To understand the mechanisms of BBB penetration, and to enable a function-first screening approach in human cell systems, we have developed organ-on-chip technologies and advances in 3D cell culture to model the human BBB in vitro.

11:25 The OrganoPlate: Human Organ-on-a-Chip Tissue Models for Predictive Drug Testing in High Throughput

van-Vught_RemkoRemko van Vught, Director, Business Development, Mimetas B.V.

MIMETAS provides organ-on-a-chip products for compound testing, screening and fundamental research. Its flagship product, the OrganoPlate®, harbors up to 96 chips and supports 3D cell culture under continuous perfusion, with membrane-free co-culture and epithelial and endothelial tubules. MIMETAS has developed models for the kidney, liver, gut, brain and a range of oncological applications, that offer better predictivity towards human physiology as compared to laboratory animals and conventional cell culture models.

11:55 Transition to Lunch

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:30 Session Break

iPSC-DERIVED BRAIN-LIKE AND ESOPHOGIAL-LIKE 3D MODELS

1:05 Chairperson’s Remarks

Kambez H. Benam, PhD, Assistant Professor, Division of Pulmonary Sciences and Critical Care Medicine, Departments of Medicine & Bioengineering, University of Colorado

1:10 Engineering of 3-Dimensional Brain-Like Tissues to Study Neurological Disorders

Nieland_thomasThomas Nieland, PhD, Research Associate Professor, Initiative for Neural Science, Disease & Engineering (INSciDE@Tufts), Department of Biomedical Engineering, Tufts University

The enormous complexity of brain interactions makes understanding and treating neurodegenerative and psychiatric diseases more difficult than dealing with diseases in other organs. Here, I will present our tissue engineering approaches to build 3-dimensional brain circuits from iPSC derived neurons and supporting cells (e.g. microglia, astrocytes). We use these human brain-like tissues to identify disease mechanisms and drugs for autism, Alzheimer’s and Parkinson’s diseases.

1:40 3D Modeling of iPS-Derived Basal Stem Cells for Translational Studies

Jianwen Que, MD, PhD, Associate Professor, Medicine, Columbia University Medical Center

Pluripotent stem cells (PSCs) including iPS and human embryonic stem cells (hESCs) are instrumental for uncovering the mechanisms promoting diseases in multiple organ tissues. They are also useful for identifying novel drugs or compounds for therapeutic purpose. Here, we will discuss how we for the first time generate basal stem cells from PSCs and use them for 3D modeling of the development, disease of the esophagus.

2:10 Organoid Systems for Industry-Relevant Assay Endpoints

Michael Hiatt, Senior Scientist, Bioengineering, Research and Development, STEMCELL Technologies

2:25 Refreshment Break in the Exhibit Hall with Poster Viewing

AT THE INTERFACE OF ENGINEERING AND RESPIRATORY MEDICINE: UPDATES AND APPLICATIONS

3:10 Modeling Human Airway Diseases in Three Dimension: Introducing Small Airway-on-a-Chip and Breathing-Smoking Lung-on-a-Chip Microfluidic Technologies

Benam_KambezKambez H. Benam, PhD, Assistant Professor, Division of Pulmonary Sciences and Critical Care Medicine, Departments of Medicine & Bioengineering, University of Colorado

This session will focus on cellular and tissue engineering approaches in the pulmonary field. It will explore a variety of approaches including microfluidic organ engineering methods like lung-on-a-chip, as well as matrix-based re-cellularized tissues. This session will also discuss application of such approaches for disease modeling, drug testing, biomarker discovery and regenerative medicine.

3:40 Fibrotic Microtissue Array to Predict Anti-Fibrosis Drug Efficacy

Zhao_RuogangRuogang Zhao, PhD, Assistant Professor of Biomedical Engineering, Department of Biomedical Engineering, State University of New York at Buffalo

A major bottleneck in developing new anti-fibrosis therapies is the lack of in vitro models that recapitulate dynamic changes in tissue mechanics during fibrogenesis. Here we create membranous human lung microtissues to model key biomechanical events occurred during lung fibrogenesis. With these capabilities, we provide proof of principle for using this fibrotic tissue array for multi-parameter, phenotypic analysis of the therapeutic efficacy of two anti-fibrosis drugs recently approved by the FDA.

4:10 Transition to Keynote


4:20 PLENARY KEYNOTE SESSION View details

5:20 Welcome Reception in the Exhibit Hall with Poster Viewing

6:35 Find Your Table, Meet Your Moderator

6:40 Breakout Discussion Groups View details

7:30 Close of Day

Wednesday, June 19

7:00 am Registration Open and Morning Coffee

BIOPRINTING AND ORGAN-ON-A-CHIP

8:00 Chairperson’s Remarks

Ruogang Zhao, PhD, Assistant Professor of Biomedical Engineering, Department of Biomedical Engineering, State University of New York at Buffalo

8:05 Putting 3D Bioprinting to the Use of Tissue Model Fabrication

Zhang_YuShrikeYu Shrike Zhang, PhD, Assistant Professor, Associate Bioengineer, Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School & Harvard-MIT Division of Health Sciences and Technology

The talk will discuss our recent efforts on developing a series of bioprinting strategies including sacrificial bioprinting, microfluidic bioprinting, and multi-material bioprinting, along with various cytocompatible bioink formulations, for the fabrication of biomimetic 3D tissue models. These platform technologies, when combined with microfluidic bioreactors and bioanalysis, will likely provide new opportunities in constructing functional microtissues with a potential of achieving precision therapy by overcoming certain limitations associated with conventional models based on planar cell cultures and animals.

8:35 3D Bio-Printed Vascularized Glioblastoma Model for Drug Discovery

Lee_VivianVivian K. Lee, PhD, Postdoctoral Research Associate, Department of Bioengineering, Northeastern University

Glioblastoma (GBM), the most malignant brain cancer, remains deadly despite wide-margin surgical resection and concurrent chemo- & radiation therapies. Two pathological hallmarks of GBM are diffusive invasion along brain vasculature, and presence of therapy-resistant tumor initiating stem cells. However, the lack of proper 3D models that recapitulate GBM hallmarks restricts investigating cell-cell/cell-molecular interactions in tumor microenvironments. In this study, we have created GBM-vascular niche models that can recapitulate various GBM characteristics such as cancer stemness, tumor type-specific invasion patterns, and drug responses with therapeutic resistance.

9:05 Sponsored Presentation (Opportunity Available)

9:35 Coffee Break in the Exhibit Hall with Poster Viewing

10:20 Chemoselective Functionalization of Native Biomaterials for 3D Tissue Engineering

Ren_XiXi Ren (Charlie), Assistant Professor, Biomedical Engineering, Carnegie Mellon University

Decellularized native extracellular matrix (ECM) biomaterials are widely used in tissue engineering. We have developed a metabolic labeling approach to incorporate click-reactive azide ligands into the ECM of a wide variety of tissues and organs in vivo and ex vivo. These incorporated azides served as chemoselective ligands for subsequent bioconjugation via click chemistry. The resulting clickable native biomaterials can be used to immobilize desired biomolecules while maintaining their bioactivity.

10:50 CO-PRESENTATION: Engineering Reproduction: Microfluidic and Tissue Engineering Approaches for Female Fertility

Emma S. Gargus, MD/PhD Candidate, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University

Rogers_HunterHunter B. Rogers, PhD Candidate, Ob/Gyn, Feinberg School of Medicine, Northwestern University

Advances in biomedical engineering have enabled the development of models for studying and restoring female fertility. Our laboratory created the first ex vivo model of the female reproductive tract, which recapitulated the 28-day human menstrual cycle, and has been a pioneer in ovarian tissue engineering from alginate to decellularized ovarian scaffolds and recently, the first 3D-printed bioprosthetic ovary, which restored both endocrine function and physiologic fertility in ovariectomized mice.

11:20 PANEL DISCUSSION: Organs on a Chip – versus Bioprinting

Moderator: Yu Shrike Zhang, PhD, Assistant Professor, Associate Bioengineer, Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School & Harvard-MIT Division of Health Sciences and Technology

Speakers of the Session

  • Pros and cons of each technique
  • Integrating the two together
  • Future directions for 3D modeling

11:50 Transition to Lunch

NanosurfaceBiomedical12:00 pm Bridging Luncheon Presentation to be Announced

 

12:30 Transition to Plenary


12:50 PLENARY KEYNOTE SESSION View details

2:20 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing

3:05 Close of Conference

Stay on to attend Wednesday, June 19 - Thursday, June 20

Applying 3D Models

Recommended Short Courses

SC3A: Development of Micro Physiological Systems for Drug Screening
SC6: Targeted Protein Degradation Using PROTACs and Molecular Glues