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
8:00 Chairperson’s Remarks
John Lowman, Partnerships and Innovation, 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
Hansjoerg
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
10:25 Blood-Brain-Barrier Organoids for Modeling the Permeability of CNS Therapeutics
Choi-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
Graham 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
John Lowman, Partnerships
and Innovation, 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 Enjoy Lunch on Your Own
12:30 Session Break
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
Thomas 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 Choosing The Right Level Of Physiological Relevance In Your in vitro Model
Michael Hiatt, Senior Scientist, Bioengineering, Research and Development, STEMCELL Technologies
2:25 Refreshment Break in the Exhibit Hall with Poster Viewing
2:30 - 2:45 Speed Networking: Young Professionals
3:10 Modeling Human Airway Diseases in Three Dimension: Introducing Small Airway-on-a-Chip and Breathing-Smoking Lung-on-a-Chip Microfluidic Technologies
Kambez 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
Ruogang 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
5:20 Taste of New England Welcome Reception in the Exhibit Hall with Poster Viewing
5:25 Meet the Plenary Keynotes
6:25 Find Your Table, Meet Your Moderator
6:30 Breakout Discussion Groups
7:30 Close of Day
Wednesday, June 19
7:00 am Registration Open and Morning Coffee
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
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
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
Vivian 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 CO-PRESENTATION: The Age of Applications in 3D Bioprinting
Taciana Pereira, Director of Bioengineering, Allevi, Inc.
Ricky Solorzano, CEO, Allevi, Inc.
Biology exists in 3D, but it is most often studied in oversimplified 2D experiments. Extrusion bioprinting offers a series of standardized, automated, and high-throughput methods that allow for the creation of relevant 3D models within tissue engineering
and pharmacology. This presentation will review the key bioprinting methods that are empowering researchers around the world.
9:35 Coffee Break in the Exhibit Hall with Poster Viewing
10:05 Poster Winner Announced
10:20 Chemoselective Functionalization of Native Biomaterials for 3D Tissue Engineering
Xi 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
Hunter B. Rogers,
PhD, 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
Panelists: Ruogang Zhao, PhD, Assistant Professor of Biomedical Engineering, Department of Biomedical Engineering, State University of New York at Buffalo
Emma S. Gargus, MD/PhD Candidate, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University
Hunter B. Rogers, PhD, Ob/Gyn, Feinberg School of Medicine, Northwestern University
Xi Ren (Charlie), Assistant Professor, Biomedical Engineering, Carnegie Mellon University
- Pros and cons of each technique
- Integrating the two together
- Future directions for 3D modeling
11:50 Transition to Lunch
12:00 pm Bridging Luncheon Presentation Structural Maturation in the Development of hiPSC-Cardiomyocyte Models for Pre-clinical Safety, Efficacy, and Discovery
Nicholas Geissse, PhD, CSO, NanoSurface Biomedical
Alec S.T. Smith, PhD, Acting Instructor, Bioengineering, University of Washington
hiPSC-CM maturation is sensitive to structural cues from the extracellular matrix (ECM). Failure to reproduce these signals in vitro can hamper experimental reproducibility and fidelity. Engineering approaches that address this gap typically trade off
complexity with throughput, making them difficult to deploy in the modern drug development paradigm. The NanoSurface Car(ina)™ platform leverages ECM engineering approaches that are fully compatible with industry-standard instrumentation including
HCI- and MEA-based assays, thereby improving their predictive power.
12:30 Transition to Plenary
12:50 PLENARY KEYNOTE SESSION
2:20 Booth Crawl and Dessert Break in the Exhibit Hall with Poster Viewing
2:25 Meet the Plenary Keynotes
3:05 Close of Conference