Emulate - Brendan Mulrooney
Emulate is a biotechnology company located in Boston that manufactures organ-on-a-chip technologies. Organ-on-a-chip refers to a microfluidic device that houses cells in a biomimetic fashion to recapitulate the environment found in the organs in the human body. This technology has garnered a lot of attention due to the many cases of testing done in animals that did not translate into successful clinical trials in humans. The differences in biology between humans and other animals and the lack of other valid in vitro models naturally paved the way for new technologies like this to arise.
Organ-on-a-chip technology allows for a more accurate model of the human body because they can use human cell lines, replicate the structure and physiology better than simple petri dish models, and can even have additional forces that are found in the body, like the pressure from breathing, applied on the chips to properly mimic the environments we find naturally in biology. Further, the chips can be connected to each other to create an even more complex environment and replicate the interactions we see between different organs in the body. These factors combined will give researchers a easier model to manipulate to test drugs and a better idea as to whether or not the results they collect will translate into the human body.
Emulate was founded from the Wyss Institute for Biologically Inspired Engineering at Harvard University by Donal Igner, Daniel Levner, and James Coon. It was at the Wyss Institute that they developed the organs-on-a-chips technology and then went on to commercialize their innovation for mass production. The first models included chips that replicated the function of the liver, gut, kidney and bone marrow.
Since their foundation, Emulate has developed many products to replicate the environments found in the body. Current listed products include brain-chips, colon intestine-chips, duodunem intestine-chips, kidney-chips, liver chips, and lung chips. Each chip serves a specific function. The brain chip responds to inflammatory stimuli and has the morphological and functional characteristics of the blood brain barrier, making it a good model for investigating anti inflammatory drug candidates. The colon-intestine chip is also an inflammation model chip. The lung chip properly models the structure of the lungs by having both air and blood pathways in contact with the cells. The kidney and liver chips offer a model to test drug toxicity, and the duodenum chip offers a model for drug absorption. Each of these chips provides better display of physiological functions than static cell culture or organoids because they lack shear stress caused by flow. This impacts cell differentiation and ability for long-term culture.
The Brain-Chip offers a more complete model of the brain through its integration of 5 cell types including neurons, astrocytes, pericytes, microglia, and brain microvascular endothelial-like cells.The incorporation of flow and cells that comprise part of the blood brain barrier provides low barrier permeability comparable to values in vivo.
The main aspect of the Lung-Chip that sticks out is the air-liquid interface that exposes cells to relevant fluid and air that cells are normally exposed to in the lungs. The Lung-Chip also has a co-culture of two cell types, primary human lung epithelial and endothelial cells. Cell-cell interactions, flow, and stretch improve functionality, resulting in in vivo-like cell differentiation, cilia behavior, mucociliary clearance, and a tight epithelial barrier. The ability to stretch the chips allows researchers to expose the chips to relevant mechanical forces found in the lungs caused by peristalsis. All of these factors together result in a dynamic lung-like microenvironment.
The kidney-chip provides a model of the proximal tubule-peritubular capillary interface, a functional unit of the kidneys. It includes primary human proximal tubule epithelial cells and renal microvascular endothelial cells in co-culture, allowing for cell-cell interactions found in vivo. The introduction of media flow through the chip leads to greater polarization, cell height, and cilia formation than kidney epithelial cells in other methods of culture. The chip claims to be able to maintain functionality for up to 14 days.
The Colon Intestine-Chip's main appeal is the inclusion of pre-qualified biopsy-derived primary organoids and colonic endothelial cells that are placed in an environment to mimic in vivo physiology. In this environment, cells differentiate into characteristic populations and structures, allowing the formation of the intestinal barrier and microvilli seen in the body. Emulate claims the chip can be used to evaluate biochemical, genetic, and cellular responses in drug safety assessments, physiology and function studies, and disease modeling. Because of its accurate recreation of the colon intestine's morphology, the chip can recreate several key mechanisms of inflammation to create a solid model to study causes of inflammation. The chip responds to pro-inflammatory cytokines, and the response can be measured by monitoring levels of barrier disruption, enrichment of inflammatory gene pathways, and apoptotic activation. As such, the chip can be used to investigate drug candidates to mitigate cytokine induced inflammation.
The primary goal of the duodenum intestine-chip is to study drug absorption and drug-drug interactions. It is currently the only commercial model of the human small intestine to use pre-qualified biopsy-derived primary organoids and duodenal endothelial cells, similar to Emulate's other intestine chip, the colon intestine-chip. The essential epithelial cells found in the duodenum are found in physiologically relevant ratios on the chip. These include absorptive enterocytes, enteroendocrine cells, goblet cells, and Paneth cells. Mechanical forces that mimic peristalsis are applied to the chip that improve cell morphology, functionality, and gene expression. The Duodenum Intestine-Chip contains a functional intestinal barrier with clear epithelial tight junctions and physiologically similar permeability, factors that are not generally seen in traditional cell culture.
The liver chip bridges the gap in liver toxicity studies. Drug induced liver injury is a major problem to overcome in drug development, but many methods of evaluating it fall flat due to species differences in liver toxicity and the incompleteness of other in vitro models. Current methods average around 70% proper prediction success. The liver-chip contains primary hepatocytes, stellate cells, Kupffer cells, and liver sinosoidal endothelial cells in the appropriate cytoarchitecture to replicate the structure of the liver. This makes the liver-chip a better model for liver toxicity than organoids, which may have the proper cells, but lack the necessary tissue-tissue interfaces that allow the prediction of in vivo conditions.
Emulate's commercialization of organ-on-a-chip has brought a significant amount of attention to the field of microfluidics and organoid technology for disease modeling. Their models offer a cheaper, more biologically accurate model for disease that does not require the use of animals.
Future advancements will see increases in accuracy and a bigger range of diseases that can be modeled. Placing more than one chip in a circuit will allow more diverse reactions that simulate the organs' interplay with each other, offering a high fidelity method of viewing the body's reactions.