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CHI's Predictive Functional Human Tissue Models Conference - Day 2



Friday, November 18

7:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

 

Surrogate Model Systems: How Complex Do They Need to Be?

8:15 Chairperson’s Remarks

James J. Hickman, Ph.D., Professor, Chemistry, Biomolecular Science and Electrical Engineering Director, Nanoscience Technology Center, Burnett School of Biomedical Sciences, University of Central Florida


8:20 Keynote Presentation: Translational Therapeutics Development at NIH

Christopher AustinChristopher P. Austin, M.D., Scientific Director, NIH Center for Translational Therapeutics, National Institutes of Health

The explosion in mechanistic understanding of human physiology in health and disease, exemplified by the Human Genome Project and its successors, has provided a deluge of potential new targets for therapeutic development. At the same time, evolution of technologies and operational systems for drug discovery has allowed investigators and institutions in the public sector to contribute directly to new therapeutics discovery in a more vigorous way, particularly for rare and neglected diseases. Over the last decade, the NIH has built a variety of programs which complement drug discovery efforts in the biopharmaceutical sector, principally in two areas: (a) science, technology, tool, and paradigm development to improve scientific understanding and efficiency of the therapeutics discovery process, and (b) early stage drug development programs to de-risk projects particularly for rare and neglected diseases, making them more amenable to biopharmaceutical adoption despite their low expected ROI.  The mission and accomplishments of these programs will be discussed.

9:00 Engineering Functional 3D Models: Breakout Discussion Groups

Grab a cup of coffee and join a table discussion. These focused groups are designed for conference participants to discuss important and interesting topics related to functional human tissue models. These are moderated discussions with brainstorming and interactive problem solving, allowing conference attendees from diverse areas to exchange ideas, experiences, and develop future collaborations around a focused discussion topic.

Table 1: Using Nanotechnology to Create Functional Tissue Models

Thomas J. Webster, Ph.D., Associate Professor, Engineering, Orthopedics, Brown University

• What is the current state of nanotechnology in medicine ?
• What are advantages and disadvantages of using nanotechnology in medicine ?
• What are key unanswered questions and what is the future of nanotechnology in medicine ?

Table 2: Potential Sources of Cells and Tissues that Can be Used in Tissue Models

Umut A. Gurkan, Ph.D., Postdoctoral Research Fellow in Medicine, Harvard Medical School; Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard-MIT Health Sciences & Technology

• What are the potential sources for cells? Animal or human based?
• Is there a need for autologous cells to better represent an individual’s own biological system?
• Can the discarded human cells/tissues be used as in vitro functional tissue models and what are the ethical or practical challenges and considerations?

Table 3: Can We Replace Animals with In Vitro Systems in the Drug Approval Process?

James J. Hickman, Ph.D., Professor, Chemistry, Biomolecular Science and Electrical Engineering Director, Nanoscience Technology Center, Burnett School of Biomedical Sciences, University of Central Florida

• Should we replace animals in the process? How would this be validated?
• What would prevent this from occurring? What are the hard problems?
• Should qualification of these new systems be left up to the FDA?

Table 4: Show Me the Money:  An In-Depth Look at the New Federal Initiatives on Developing Microphysiological Systems

Rosemarie Hunziker, Ph.D., Director, Tissue Engineering and Regenerative Medicine Program, National Institute of Biomedical Imaging and Bioengineering, NIH

• What are the differences between these funded projects?  Milestone-driven vs. exploratory?  Budget limitations? Preliminary data requirements?  Balance between risk and feasibility? 
• What kinds of teams are necessary and sufficient?
• How will proposals be reviewed?  What administrative requirements are critical?
This session will offer an opportunity to do a “deeper dive” on the differences between parallel efforts, and determine the best fit for your R&D.

Table 5: What's Critical to Validating Tissue Engineered Drug Development Platforms?

Jonathan Sackner-Bernstein, M.D., CEO, ExVivos, LLC; Former Associate Center Director, Technology and Innovation, Center for Devices and Radiological Health, FDA 

• How can we identify the needs of industry for funders and technology developers to assure utilization?
• What appear to be DARPA's high priorities?
• When does the FDA play a role, and how can it be an ally in transforming drug development paradigm?

Table 6: Induced Pluripotent Stem Cells: Can They Find a Home in 3D Tissues?

Jonathan Garlick, D.D.S., Ph.D., Professor and Director, Center for Integrated Tissue Engineering, Tufts University School of Dental Medicine, School of Medicine and School of Engineering

• What advantages or disadvantages might iPSC-derived cells have in the construction of 3D tissue models?
• What unique benefits does the field of 3D tissue models have to offer the field of iPSC biology?
• What strategies are needed to best develop surrogate models of human disease by combining iPSC-derived cells and 3D tissue technologies and what unique role would 3D tissues harboring iPSC-derived cells play in screening approaches leading to therapeutic development?

10:00 Networking Coffee Break in the Exhibit Hall with Poster Viewing

inSphero10:30 Drug De-Risking Using 3d Scaffold-Free Microtissues - Applications in Toxicology and Oncology

Jens Kelm, Ph.D., Co-Founder and Head, Product Development, InSphero


10:45 Magnetic Nanoparticles to Assemble Microgels as 3D Tissue Constructs

Utkan Demirci, Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School

Assembly of nano and microscale particles is of great interest. These technologies have widespread applications in various fields including electronics, nanomaterials and tissue engineering. Bottom-up tissue engineering requires novel techniques to assemble engineered functional units as building blocks at a high speed with spatial control over three-dimensional (3D) micro-architecture. We will report a magnetic assembler that utilizes nanoparticles and microgels to create 3D complex multi-layer constructs via external magnetic fields. This approach holds potential for 3D assembly processes that could be utilized in various tissue engineering, drug discovery, and regenerative medicine applications.

11:15 Bioprinting 3D in vitro Model for Tissue Science and Engineering

Wei Sun, Ph.D., Professor, Mechanical Engineering, Drexel University; Professor, Mechanical Engineering, Tsinghua University

Bioprinting living cells for constructing 3D models has found a broad application in 3D biology, disease study and drug testing. This presentation will introduce a novel engineering cell assembling process and application examples of assembled 3D biological models to tissue engineering and for drug metabolism and cancer studies.

11:45 Using Nanotechnology to Create Functional Tissue Models

Thomas J. Webster, Ph.D., Associate Professor, Engineering, Orthopedics, Brown University

Nanotechnology, or the use of materials with fundamental length scales less than 100 nm, have begun to revolutionize regenerative medicine. In this talk, efforts to use nanomaterials to create functional tissue models will be covered. This includes the creation of nanostructured polymers, ceramics, and metals. Tissue models to be covered include the heart, bone, cartilage, tendons, ligaments, bladder, vascular, and nervous system. Such in vitro models using nanomaterials have been shown to more accurately predict in vivo responses.

12:15 pm Close of Session

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

 

Tissue Models for Drug Discovery & Development:
Ready for prime time?

1:45 Chairperson’s Remarks

Jonathan Garlick, D.D.S., Ph.D., Professor and Director, Center for Integrated Tissue Engineering, Tufts University School of Dental Medicine, School of Medicine and School of Engineering

1:50 From Tissue Model to Pre-Clinical Decision Making Information

Linda Griffith, Ph.D., Professor, Biological and Mechanical Engineering, MIT

2:20 A Three-Dimensional Multi-Compartment Bioreactor for Studies of Human Hepatic Functions

Marc Lübberstedt, Dipl. Ing. Biotech., Division of Experimental Surgery, Berlin Brandenburg Center for Regenerative Therapies, Charite University Berlin

The multi-compartment hollow fiber liver bioreactor developed for extracorporeal liver support has successfully been scaled down to a useful size for pre-clinical studies of human liver functions such as drug metabolism and drug-drug interactions. The bioreactor inoculated with primary human hepatocytes or with the human hepatoma cell line HepaRG exhibits stable liver like functions for several weeks,which opens up for a range of applications in pre-clinical drug testing.

2:50 A Microfluidics-Based Model for Drug-Induced Vascular Injury

Jeffrey Borenstein, Ph.D., Director, Biomedical Engineering, Charles Stark Draper Laboratory

Drug-Induced Vascular Injury (DIVI) represents a daunting regulatory challenge in drug development; in vitro models capable of assessing compounds for potential vascular injury are urgently needed, as animal models for DIVI are neither sufficiently reliable nor predictive. Here we describe the development of a microfluidics-based blood vessel model capable of replicating the structural and hemodynamic microenvironment of in vivo vasculature. The model incorporates endothelial and smooth muscle cells in a membrane bilayer device with blood flow through the endothelialized artificial vascular network. Initial results indicate that the model is capable of distinguishing control molecules from compounds known to induce vascular injury in animal models.

3:20 Selected Oral Poster Presentation
Modeling the Tumor-Vascular Microenvironment Using 3D Microfluidic Matrices

Ioannis Zervantonakis, Ph.D. Candidate, Department of Mechanical Engineering, Massachusetts Institute of Technology

Compared with traditional in vitro assays, microfluidic-based platforms enable a “user-defined” design of the cellular and acellular microenvironment with spatio-temporal control, while also allowing for integration of real-time high resolution imaging. In this study, we present a novel tumor-endothelial interaction assay which enables to study simultaneously cancer cell intravasation dynamics and endothelial barrier function in 3D. The assay validity was demonstrated by showing an increase in intravasation efficiency and endothelial monolayer leakiness upon stimulation with TNF-α. Ongoing work includes investigation of the role of additional cell types (e.g. macrophages) and correlation between these two measures, which will provide insight into the roles of the endothelial cells and microenvironmental factors during intravasation

3:35 Networking Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 Tissue Models to Investigate Cell-Matrix Interactions in Cancer

Shelly Peyton, Chemical Engineer, University of Massachusetts, Amherst

Our lab seeks to understand the fundamental aspects of how cells process complex information from a dynamic matrix environment in order to achieve functional phenotype. Within the cancer microenvironment, the dysregulated matrix includes dynamic physical and chemical cues, which we attempt to capture with 2D and 3D biomaterial model systems. In this talk, we will discuss our work on how cell migration (metastasis) and drug resistance are regulated by tissue stiffness and adhesive protein cues.

4:30 Biomimetic Microsystems Technologies: Organs-on-Chips

Geraldine Hamilton, Ph.D., Senior Staff Scientist, Wyss Institute for Biologically Inspired Engineering at Harvard University
Biomimetic ‘Organ-on-Chip’ microsystems technologies that recapitulate organ-level functions offer exciting new approaches to attack fundamental questions in biology, create smart medical devices, and develop in vitro surrogates for regulatory sciences that can positively impact human health.  These engineered cell culture microenvironments go beyond conventional three-dimensional in vitro models by recapitulating the tissue-tissue interfaces, spatiotemporal chemical gradients, and mechanical microenvironments of living organs.  By integrating human cells within Organs-on-Chips as in our ‘Breathing Lung-on-a-Chip,' human physiology can be studied in an organ-specific context; this also facilitates development of specialized in vitro disease models.  The presentation will also highlight the potential application of these systems as more predictive human-relevant alternatives in drug discovery where rapid determination of the efficacy and safety of new chemical entities is of critical importance.

5:00 Form Informs Function: 3D Human Tissue Models Constructed from Stem Cells, Cell Lines and Induced Pluripotent Stem Cells

Jonathan Garlick, D.D.S., Ph.D., Professor and Director, Center for Integrated Tissue Engineering, Tufts University School of Dental Medicine, School of Medicine and School of Engineering

3D tissue platforms will have a direct impact on the decision to proceed with clinical trials by providing information with significantly higher predictive value for success in human disease treatment than currently existing 2D, cell-based assays. This presentation will describe such tissue models and ways they have been applied to demonstrate the potential of this approach. Construction of a broad spectrum of 3D tissues harboring either tissue-specific stem cells, widely-available cell lines and cells derived from induced pluripotent stem cells will illustrate how such tissue and disease models can move us from "disease in a dish" to "disease in a tissue."

5:30 Close of Conference



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Group Discounts are Available! Register a group of 2 or more and save up to 30%. For details, contact David Cunningham at 781-972-5472.

 


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