We have designed our Organs-on-Chips technology to fully recreate the complex, dynamic state in which living cells function within a real human organ. This unique approach to developing our technology enables us to accurately recreate and modulate human biology and disease states.
True-to-Life Biology: Human Emulation
June 1, 2015
True-to-Life Biology: Human Emulation
Using engineering principles we are able to control critical aspects of the living cellular microenvironment within our Organ-Chips.
“Our team has developed working models of the lung, liver, intestine, and brain. We are also developing designs for other organ systems such as the kidney, heart, and skin.”
Our Organ-Chips recreate living human physiology. Key aspects of our system that allow us to emulate human biology include:
1) Extracellular Matrix
Cells of an organ require a physical surface so they can attach and function. This is the extracellular matrix, comprised of molecules secreted by cells that provide the structural and biochemical support to the surrounding cells in a tissue.
We recreate this key component of in vivo biology with a porous membrane in the central channel of our Organ-Chips. This membrane is coated with extracellular matrix proteins that are found in human organs and promote cell attachment and assembly.
2) Tissue-Tissue Interface
Our Organ-Chips direct the proper orientation of cells and their interactions with other neighboring cells. They are designed to produce the essential tissue-tissue interface found in living organs. This tissue is comprised of epithelial cells (organ specific cells) and endothelial cells (blood vessel capillary cells) in a physiologically relevant architecture.
3) Mechanical Forces
Our Organ-Chips emulate the physical forces that cells experience within the body. These physical forces have long been recognized as key determinants of cellular function, cell signaling, and gene expression. Mechano-transduction, as it is called, is the process by which cells sense external mechanical forces and translate them into biochemical signals that direct cell function, differentiation, and cyto-architecture.
Cells experience mechanical and fluidic forces in vivo through various mechanisms such as expansion of the lungs during breathing, peristalsis in the gut, and the flow of blood in the capillaries. In our Organ-Chips, we emulate the shear stress that arises from blood flow by pumping fluid through the microchannels. We are also able to recreate the mechanical forces cells experience during breathing by cyclically stretching the membrane within the Lung-Chip.
4) Biochemical Surroundings
The biochemical surroundings of cells are the soluble factors that provide cues for appropriate cell function and are required for cell survival. These include growth factors, hormones, dissolved gases, and small molecules such as salts and nutrients.
We can precisely recreate and control the biochemical environment within our Organ-Chips by continuously flowing blood or blood substitutes that bring in fresh nutrients, soluble factors, and dissolved gases, while washing away waste. This enables us to recreate the spatiotemporal gradients of chemicals that allow cells and tissues to thrive in vivo.
5) Immune Cells and Blood Components
Immune cells — such as white blood cells — play an important role in defending our bodies against infection and are key mediators of inflammation. Inflammation is implicated in many pathologies and disease states including asthma, diabetes, and cancer. The fluidic nature of our Organs-on-Chips technology not only allows us to bring in nutrients and gases but also enables us to introduce immune cells to the system in a manner that mimics the dynamics found in the capillaries.
This is a key advantage of our approach, allowing us to mechanistically study the role of immune cells and inflammation in health and disease in different tissues. Moreover, we can also elucidate the interaction between certain drugs and blood components.
"Precise tuning of the extracellular matrix, tissue-tissue interfaces, mechanical microenvironment, chemical surroundings, and immune components results in a biologically accurate model of human physiology."
Our Organ-Chips uniquely emulate the complex organ-level function in our bodies that require interactions and cell signaling between different cell types and tissues in a coordinated manner. This provides the opportunity to emulate normal human biology, model the different aspects of diseases, and facilitate the discovery of new treatments.
Examples of Human Emulation:
Inflammation and Immune Response:
We have used our system to recreate and quantify key aspects of inflammation and immune response in the lung after bacterial infection. In our Lung-Chip we show in real time how immune cells are recruited from the vasculature upon inflammation and observe how they enter lung tissue and engulf invading bacteria — just as they do in the human body. This provides the unique window into the mechanisms involved in the body’s immune response.
Pathology of Pulmonary Edema: In our Lung-Chip, we are able to show that the mechanical forces that simulate breathing actually made this condition worse, providing us with new knowledge about the injury mechanism. Our Lung-Chip was also used to test the efficacy of a drug candidate on pulmonary edema.
Mucociliary Clearance of Particles: We have recreated other aspects of lung biology, including mucociliary clearance of particles from the lung, which are critical for lung health and can be affected in diseases such as cystic fibrosis. We have also modeled other critical disease states such as acute inflammation in asthma and infection of our Lung-Chip with viruses.
We can create intestinal peristalsis-like motions in our human Intestine-Chip. The epithelial cells form structural folds within the chip that resemble intestinal villi. They also reconstruct a high-integrity barrier to small molecules that better recreates the intestinal barrier in the gut when compared to conventional cell culture systems. We can also introduce microbial flora to our Intestine-Chip and are able able to reproduce the beneficial effects of these probiotic bacteria on barrier function in the gut.