Organs-On- A-Chip: A Novel Approach to Studying Inflammatory Bowel Disease

Biological engineers at MIT are using a new technique to study various organs and their interaction with our immune system.

According to a recent article in Science Daily, the researchers have developed a multifluidic device which uses a small amount of fluid on a microchip for laboratory testing.

The device may use body fluids or various solutions that contain human cells for diagnosing diseases. The device is called organs(physiome)-on-a-chip.

The engineers used the multitissue model to study the effect of circulating immune cells on ulcerative colitis.

The Technology Has Been Evolving Since 2000

Linda Griffith, a biological engineering professor, is the study’s senior author. Griffith and her lab started work on a device called a “liver chip” almost twenty years ago. Griffith’s lab worked with liver tissue on a scaffold that tested drug toxicity.

Recently, Griffith has been involved with small-scale copies of interconnected organs-on-chips called microphysiological systems. These chips, using human cells, bring new tools to medicine, biology, physiology, pharmacology and toxicology.

Griffith noted that researchers can now address inflammatory diseases with experiments using organs on chips.

The novel approach was described this month in the journal Cell Systems as facilitating the study of many diseases that are complex and difficult to treat.

Martin Trapecar is the lead author of the study. Trapecar emphasizes that researchers now have more control over the degree of complexity when they study a disease.

Analyzing Complex Diseases

The organs-on-a-chip devices are effective for the analysis of complex diseases that:

  • pertain to multiple organs
  • interact with the immune system
  • are not associated with one or more genes

Griffith explains that their goal was to create technologies that enable the researchers to connect multiple organ systems. In that way new tools may be developed that would attack chronic inflammatory diseases.

She explained that in developing drugs, it has been a struggle to work with anything other than single-gene diseases.

About the Cell Systems Study

Trapecar and Griffith began researching the Cell Systems with a goal of modeling interactions between the liver and the colon. Their intent was to analyze how our immune system, specifically the T cells, affects  each organ.

The medical community is aware that almost 80% of people with primary sclerosing cholangitis, an autoimmune disease that affects the liver, are also affected by IBD (inflammatory bowel disease.)

About This New System

Colon and liver cells were gathered from patients who have ulcerative colitis. The researchers discovered that when the cells are connected, their physiological behavior changes completely.

Other changes occurred. When ulcerative colitis gut tissue was exposed to healthy liver cells, the inflammation decreased. In addition, the cellular pathways and genes that were involved in immune and metabolism function were increasingly active in the colon and liver.

The researchers were able to recreate specific features of autoimmune liver diseases and IBD with the addition of two forms of T cells. One type of T cells stimulates inflammation while the other suppresses immune cells.

Investigating short-chain fatty acids (SCFAs) and their role in inflammatory disease was last chapter in the study.

Microbes found in the human gut produce the SCFA molecules that represent ten percent of our daily energy.

Despite the many benefits of SCFAs, recent studies have found that SCFAs also stimulate inflammation. According to an MIT study, when SCFAs were added to an ulcerative colitis model it increased inflammation throughout the gut and liver but only when T cells were present.

SCFAs and Parkinson’s

The MIT study evolved from a similar project where researchers intend to research interactions of the liver, brain and gut.

In studying a mouse model, germ-free mice developed initial symptoms of Parkinson’s later than the mice that were maintained under the usual conditions.

This was an indication to researchers that SCFAs formed by microbes may contribute to disease progression.

The MIT researchers are using the system to research other diseases. Their efforts will assist in developing improved treatment for complex diseases.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.

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