Microchips lined by living human cells that could revolutionize drug development, disease modeling and personalized medicine
Clinical studies take years to complete and testing a single compound can cost more than $2 billion. Meanwhile, innumerable animal lives are lost, and the process often fails to predict human responses because traditional animal models often do not accurately mimic human pathophysiology. For these reasons, there is a broad need for alternative ways to model human diseases in vitro in order to accelerate the development of new drugs and advance personalized medicine.
Wyss Institute researchers and a multidisciplinary team of collaborators have engineered microchips that recapitulate the microarchitecture and functions of living human organs, including the lung, intestine, kidney, skin, bone marrow and blood-brain barrier. These microchips, called ‘organs-on-chips’, offer a potential alternative to traditional animal testing. Each individual organ-on-chip is composed of a clear flexible polymer about the size of a computer memory stick that contains hollow microfluidic channels lined by living human cells interfaced with a human endothelial cell-lined artificial vasculature, and mechanical forces can be applied to mimic the physical microenvironment of living organs, including breathing motions in lung and peristalsis-like deformations in the intestine. Because the microdevices are translucent, they provide a window into the inner workings of human organs.
With their ability to host and combine the different cell and tissue types making up human organs, organs-on-chips present an ideal microenvironment to mimic human-specific pathophysiologies and enable molecular and cellular scale analysis and identification of new therapeutic targets within an organ-level context in vitro. They even allow recreating therapeutically relevant interfaces like the blood-brain-barrier to facilitate discovery of new drug delivery platforms or culturing living microbiome for extended times in direct contact with living human intestinal cells to enable insights into how these microbes influence health and disease.
To mimic the interconnectedness of organs within humans, Wyss researchers also have developed an automated instrument to link multiple organs-on-chips together by their common vascular channels. This instrument, designed to mimic whole-body physiology, controls fluid flow and cell viability while permitting real-time observation of the cultured tissues and the ability to analyze complex interconnected biochemical and physiological responses across ten different organs. This holistic “human body-on-a-chip” approach will be used to rapidly assess systemic responses to new drug candidates, providing higher-level information on their safety and efficacy.
A Wyss Institute-launched startup company, Emulate, Inc. has licensed the technology and is now further developing and commercializing the Institute’s organs-on-chip technology and automated instruments to improve industrial development and personalized medicine by bringing these important research tools to widespread academic institutions as well as biotechnology, pharmaceutical, cosmetics and chemical companies.
Current work at the Wyss Institute is now focused on developing specific human disease models and leveraging the organ-on-chip platform to identify new therapeutic targets and clinical biomarkers, facilitate vaccine development, develop novel organ-specific drug delivery systems, and explore the potential of the technology for personalized medicine.
The Wyss Institute is currently seeking partners in their research and development efforts towards development of novel technologies for organ-specific targeting and drug delivery as well as clinical biomarkers and potential therapeutics that have been discovered using the organ-on-chip platform.
Figure 1: Patent Drawing of Original Lung on a chip Design
Figure 2: The Lung-on-a-Chip offers an in vitro approach to drug screening by mimicking the complicated mechanical and biochemical behaviors of the human lung.
Figure 3: Lung-on-a-Chip sitting on a microscope, connected to vacuum and flow channels.
Figure 4: The Organs-on-Chips are crystal clear, flexible polymers about the size of a computer memory stick that contain hollow channels fabricated using computer microchip manufacturing techniques. These channels are lined by living cells and tissues that mimic organ-level physiology..
Figure 5: High resolution scan of a Gut-on-a-Chip.
Figure 6: The Wyss Institute's human gut-on-a-chip precisely mimics the biochemical and mechanical microenvironment of the human intestine, even expanding and contracting cultured human intestinal epithelial cells just as they would do rhythmically inside the gut through the process of peristalsis, as seen here. It is an ideal platform for studying the gut, the gut microbiome that thrives inside it, and for developing innovative new therapies to treat infection and disease of the intestinal tract..