Recently, biological engineers at the Massachusetts Institute of Technology (MIT) created a model called “organs on the chip.” This is a multi-tissue model that allows them to study the relationship between different organs and the immune system on a dedicated microfluidy platform. Using this model, the team was able to explore the role of circulating immune cells in ulcerative colitis and other inflammatory diseases.
They also found that metabolic by-products produced by bacteria living in the human gut play an important role in these inflammatory conditions.
The study, published in Cell Systems, could also be used to study many other complex diseases.
About 20 years ago, the lab of Linda Griffith, senior author of the study and professor of teaching innovation at the School of Engineering and professor of bioengineering and mechanical engineering, first began working on a model of the human liver known as a “liver chip.” The system consists of artificial liver tissue grown on a special stent and can be used for drug toxicity testing.
More recently, she has been studying small replicas of many interconnected organs, also known as microphysiological systems (MPS). In 2018, she developed a platform that could be used to simulate interactions between up to 10 organs at a time.
(Picture: 2016 report on tiny human organs on this chip.) Source: MIT)
(Figure: They present a concept diagram of the full-body bionic device “The Man on the Chip.” Source: MIT)
In 2016, the chip was made from a flexible polymer characterized by microfluidic channels and seven deep wells that hold organ materials. These wells are filled with living organ tissue grown from stem cells, or collected in surgery, and then grow on a three-dimensional stent, allowing tissue to adopt natural three-dimensional structures found in the human body.
As in the human body, the organs on the chip provide oxygen and food by pumping through a liquid rich in oxygen. Researchers will be able to monitor the effects of the drug on the chip to see if it is beneficial or harmful to different organs or the system as a whole.
These devices are ideal for analyzing complex diseases, including those that involve multiple organs, are affected by the immune system, or cannot be explained by a single gene or a few genes.
“We wanted to build a technology that would allow you to connect several organ systems so we could start developing new tools to fight chronic inflammatory diseases,” Griffith said. “
In the new study, she and Trapecar began building a model of interaction between the two organs, the colon and the liver. They also want to study how the immune system, especially T-cells, affects these organs.
It is well known that up to 80% of patients with chronic liver autoimmune disease (primary sclerosing bile ductitis) also suffer from inflammatory bowel disease (IBD). Moreover, patients with IBD are much more likely to develop an autoimmune disease in the liver.
The new system includes colon cells extracted from patients with ulcerative colitis, as well as healthy liver cells. The researchers found that when these tissues were connected, their physiological behavior was completely different from when they were separated.
Inflammation decreases after ulcerative colitis intestinal tissues are exposed to healthy liver cells. At the same time, genes and cellular pathways involved in metabolic and immune functions become more active in both organs.
The researchers then added two types of T-cells to the system: CD4-T-regulating cells, which inhibit other immune cells; TH17 cells, which stimulate an inflammatory response.
By adding these T cells to the visceral-liver interaction, the inflammatory response can quickly increase, reproducing certain characteristics of IBD and autoimmune liver disease.
Finally, the researchers decided to study the potential role of short-chain fatty acids (SCFAs) molecules in inflammatory diseases. These molecules are produced by microorganisms in the human gut.
Although these compounds have many beneficial effects on the human body, including reducing inflammation, several studies in recent years have shown that SCFAs can also cause harm by stimulating inflammation.
The new study by the Massachusetts Institute of Technology found that adding SCFAs to ulcerative colitis models significantly increases inflammation in the liver and intestines, but only if T cells already exist.
“Based on these studies, we have formed the assumption that the role of short-chain fatty acids seems to depend on the level of participation of the adaptive immune system, including T-cells,” Trapecar said.
In other words, in the early stages of inflammation, SCFAs can help reduce inflammation when T cells are not heavily involved.
But when many effect T cells are collected, SCFAs stimulate them to produce more inflammation.
This may be useful in the case of infection and helps the body fight off intruders, but it can also accelerate autoimmune diseases.
Griffith’s lab is now working on using the MPS system to clarify the link between SCFAs and Parkinson’s disease.
The researchers also plan to study other complex diseases, hoping their findings will help guide the development of new treatments for currently difficult-to-treat diseases.
The study was funded by the U.S. Defense Advanced Research Projects Agency, the National Institutes of Health, the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Environmental Health Sciences, the Koch Institute of the National Cancer Institute and the Pell-Stewart Trust.
“Another way” for artificial organs
There have been many experiments on artificial organs, but the methods used by the researchers vary.
The “artificial pig lung” produced by the University of Texas School of Medicine in the United States uses a different approach. They first cleaned all the cells and blood in the pig’s lungs through sugar, detergent and other supplies, leaving only the protein as the “skeleton” of the lung organ, then adding cells extracted from the pig’s lungs on each stent, and placing the lung stent in a pool filled with special nutrients to create a real pig lung. This form actually uses natural organ structures.
Scientists at Carnegie Mellon University in the United States have reported that 3D bioprinting technology replicates the structure of the human heart, using natural collagen for 3D printing bio-inks. This 3D printing technique is based on gelatin as a support bed, allowing collagen to be deposited and solidified layer by layer in the support ingresin. After the print is done, the researchers then change the temperature to allow the gelatin for the support to melt.