Polymers on Front Lines of Asthma Research

AsthmaLab-on-a-chip technology using polymers can speed testing of therapies for asthma. is a chronic respiratory disease that affects the airways or bronchial tubes of the lungs. The airways of asthma sufferers are chronically inflamed and can become narrower when something triggers an asthmatic response. This contraction will cause symptoms such as coughing, wheezing, shortness of breath, and chest tension. In the U.S., one person in 12 is affected by asthma.

The drugs used to treat asthma today are mostly the same ones used 50 years ago. New drugs and treatments are needed to help those who suffer from this chronic respiratory disease. There are difficulties in finding new therapies because asthma is patient-specific — a treatment that works well for one patient may not work at all in another. The use of animal models for finding new drugs is challenging because animals don’t produce the same responses as humans.

Lab-on-a-Chip

Scientists at Harvard University’s School of Engineering and Applied Sciences have found a way to mimic asthma by using lab-on-a-chip technology. Alexander Peyton Nesmith leads a research team that has developed an airway muscle-on-a-chip. Its layers dilate and contract, increasing and decreasing their width. The chip uses human bronchial smooth muscular thin films (bMTFs) to create the response needed. The bottom layer of the device uses a layer of flexible polymer polydimethylsiloxane (PDMS), with a layer of engineered bronchial smooth muscle resting on top. Contraction of the muscle layer causes the bMTF to bend, thereby decreasing the curve of the tissue.

The group used interleukin-13 (IL-13), a protein usually found in the airways of asthma patients that initiates reaction of the smooth muscle when an allergen is present. Acetylcholine, a neurotransmitter, was added to elicit an allergic response by causing the smooth muscle to contract. When high doses of acetylcholine were introduced, the smooth muscle overly contracted and curled up. Beta-agonists, often found in asthma inhalers, were then used on the chip, and the muscle relaxed. When the chip was exposed to different drugs and doses, the research team was able to examine and accurately measure the human reaction to an asthma stimulus.

Mimicking Symptoms

In asthma patients, extended exposure to IL-13 causes enlargement of smooth muscle cells, which leads to a thickening of the airway wall, narrowing the airway. Added alignment of actin fibers in the smooth muscle cells is also characteristic among asthma patients. The researchers were able to mimic these symptoms of longtime asthma sufferers using the chip.

The team then looked at IL-13 to determine how it affected RhoA proteins. This protein helps control bronchial smooth muscle contraction although it isn’t clear exactly how. They introduced a drug called HA1077 that targets the RhoA pathway. The results illustrated the muscle tissue on the chip that was exposed to IL-13 had a reduced responsiveness to asthma stimuli. The researchers explained:

This result indicates HA1077 decreases the basal tone of our engineered bronchial smooth muscle tissue and prevents hypercontraction.

The group went on to explore the effects of HA1077 combined with a known asthma drug, isoproterenol. The combination of the two was more successful at limiting reactions to asthma stimuli than isoproterenol on its own, showing the chip’s potential for finding novel therapies for asthma relief.

Donald Ingber, a professor or bioengineering at Harvard’s School of Engineering and Applied Sciences and founding director of the Wyss Institute at the university said:

Asthma is one of the top reasons for trips to the emergency room, particularly for children, and a large segment of the asthmatic population doesn’t respond to currently available treatments. The airway muscle-on-a-chip provides an important and exciting new tool for discovering new therapeutic agents.

As We Live and Breathe

This type of lab-on-a-chip technology is poised to change the world of research. The reactions are more closely related to the dynamics of the human body because they use the same tissue. Subsequently, the novel treatments and drugs resulting from lab-on-a-chip experiments could be more effective than those developed using computer simulated or lab animal experiments.

Today’s technologies are changing health care by cutting costs, reducing risk, and creating more effective and personalized treatment than ever before.

Image by tribalium123/123RF.
Source: “Asthma Overview,” American Academy of Allergy Asthma and Immunology, https://www.aaaai.org, 2014.
Source: “Airway Muscle-on-a-Chip Mimics Asthma,” by Kristen Kusek, https://www.seas.harvard.edu, September 23, 2014.
Source: “Airway Muscle-on-a-Chip ‘Simulates Asthma in Humans,’ ” by Honor Whiteman, https://www.medicalnewstoday.com, September 24, 2014.
Source: “New Airway Muscle-on-a-Chip Could Improve Asthma Research,” by Brooks Hays, www.upi.com, September 24, 2014.
Source: “Airway Muscle-on-a-Chip Could Lead to Better Asthma Treatments,” by Rebekah Marcarelli, www.hngn.com, September 24, 2014.
Source: “Human Airway Musculature on a Chip: An In Vitro Model of Allergic Asthmatic Bronchoconstriction and Bronchodilation,” by Alexander Peyton Nesmith, et al., Lab on a Chip, August 05, 2014, DOI: 10.1039/C4LC00688G.