Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Organ-on-a-Chip Technologies: Advances and Challenges
Martin Yarmush, Paul and Mary Monroe Chair, Distinguished Professor of Biomedical Engineering, Rutgers University; Director, Center for Engineering in Medicine, Massachusetts General Hospital, United States of America

Move Over, Mice — How the Fusion of Systems Biology with Organs on Chips May Humanize Drug Development
Linda Griffith, Professor, Massachusetts Institute of Technology (MIT), United States of America

“Mice are not little people” – a refrain becoming louder as the strengths and weaknesses of rodent models of human physiology and disease become more apparent.  At the same time, three emerging approaches are headed toward integration:  powerful systems biology analysis of intra- and inter-cellular signaling networks in patient samples; 3D tissue engineered models of human organ systems, often made from stem cells; and microfluidic devices that enable living systems to be sustained and used for models like cancer metastasis.  This talk will highlight the integration of these rapidly moving fields to understand difficult clinical problems, and will especially highlight intellectual and technical challenges in transitioning “organs on chips” platforms from academic publications into practical use.

Creating Vascularized Tissue Constructs in Microfluidic Assays
Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT), United States of America

Vascularization is critical to most tissues, yet developing a perfusable microvascular network within an on-chip tissue construct has proved challenging. Several approaches have been developed in recent years including the casting of networks within a hydrogel matrix that can subsequently be lined with vascular cells, and the growth of networks from cells seeded either on the surface of a hydrogel by angiogenesis, or from cells suspended in gel by a process akin to vasculogenesis.  Our previous work has followed the second path in producing networks within microfluidic platforms that can be perfused within several days of seeding.  These networks can be grown in various matrices either in co-culture with other cell types such as fibroblasts, myoblasts or osteoblasts, or in isolation.  To date, the best results have been obtained by co-culture with normal lung fibroblasts in separate gel regions, using a fibrin-based extracellular matrix.  Recently, these systems have been scaled up to mm-sized regions and the fibroblasts are co-seeded with the endothelial cells, leading to vascularized and perfusable networks that are perfusable for three weeks with potential applications for in vitro organ-on-chip systems.

Organs-On-Chips for Advancing Drug Development and Personal Health
Geraldine A Hamilton, President/Chief Scientific Officer, Emulate Inc, United States of America

This talk discusses emulating living human biology to understand how different diseases, medicines, chemicals and foods affect human health. These systems are being used to advance product innovation, design and safety across a range of applications – including drug development, agriculture, cosmetics, chemical-based products and personalized health.

Using Human “Body-on-a-Chip” Devices to Aid Drug Development
Michael Shuler, Samuel B. Eckert Professor of Engineering, Cornell University; President & CEO, Hesperos, Inc., United States of America

Effective human surrogates constructed from a combination of human tissue engineered constructs, microfabricated devices, and PBPK (physiologically based pharmacokinetic) models offer a potential alternative or supplement to animal studies to make better decisions on which drug candidates to move into clinical trials. These systems have been called microphysiological systems. We have constructed “pumpless” systems that provide a low cost, relatively simple-to-use platform to evaluate potential drugs for human response. In addition to measuring viability and metabolic responses, we can measure functional outputs such as electrical activity and force generation (in collaboration with J. Hickman, University of Central Florida). We will focus our discussion on development of key organ modules and their integration into a model of the whole body.

Microengineered Systems for Recapitulating Intestinal Function
Nancy Allbritton, Professor and Chair, University of North Carolina, United States of America

Technical advances are making it possible to create tissue microenvironments on platforms that are compatible with high-content screening strategies. We have developed a microfabricated device to enable culture of organized cellular structures possessing much of the complexity and function of intact intestinal tissue.  Single stem cells or crypts isolated from primary mouse intestine grow and persist indefinitely as organotypic structures containing all of the expected lineages of the intestinal epithelium. Our microengineered arrays and fluidic devices allow prolonged culture and experimental manipulation of these intestine-on-chip systems.  Millimeter-scale primary intestinal epithelium can be formed closely mimicking the polarized 3D in vivo microarchitecture of primary tissue. These systems can also be interrogated by a variety of techniques including fluorescence, immunohistochemistry and genetic analyses. The bioanalytical platforms are envisioned as next generation systems for high-throughput assays of drug- and toxin-interactions with the intestinal epithelia.

LiverChip – Development of Organ-on-a-chip Liver Disease Models
David Hughes, Chief Technical Officer, CN Bio Innovations Ltd., United Kingdom

Organ-on-a-chip (OOC) technologies offer the promise of in vitro models which more closely recapitulate the in vivo. Current OOCs typically have low to medium throughput, offer high information content and are relatively complex when compared to 2D cultures, making it more likely that these technologies could replace certain animal tests than supplant high throughput screens. An initial wave of activity focused on drug metabolism and safety applications of OOCs however an animal-centric regulatory framework, particularly for safety testing, and a disconnect between the cost and benefit that OOCs can provide in ADME/Tox make this a challenging area in which to achieve widespread adoption. Disease modelling provides a more compelling opportunity for OOC technologies: a number of diseases are poorly recapitulated in animal models so OOCs offering improved translational relevance would be highly desirable.  A small airway-on-a-chip to model COPD and asthma, and a hepatitis B infected liver-on-a-chip model are two examples of disease OOCs already being exploited by pharmaceutical companies in the development of new drugs. This presentation will describe the development of models for viral hepatitis, malaria and non-alcoholic fatty liver disease (NAFLD) building on a microfluidic OOC platform, LiverChip®.  Liver disease represents a significant and growing global health burden, being the only one of the top five causes of death to have increased in the UK in the last decade. The liver is a complex organ, comprised of multiple cell types undertaking hundreds of essential functions and is a major site of drug metabolism and toxicity. The liver is also a unique immunological organ in which liver resident macrophage (Kupffer) cells and lymphocytes play critical roles in first line immune defence against invading pathogens, modulation of liver injury and recruitment of circulating lymphocytes.

The NIH Tissue Chip Program: Current Progress and Future Initiatives
Kristin Fabre, Scientific Program Manager, NIH National Center for Advancing Translational Science (NCATS), United States of America

The Tissue Chip Program is comprised of several academic and government entities, aimed to bioengineer micro-physiological platforms (or chips) that mimic human organ systems.  These MPS platforms would be utilized for predicting efficacy and toxicity of candidate compounds faster, cheaper and with less use of animal models compared with current methods.  Now approaching the final year of the program, organ platform integration, rigorous testing and building public-private partnerships are the primary goals, setting the stage for future proposed initiatives including disease modeling.