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Chip Emulates Human Airway Muscles to Test Asthma Treatments

Kevin Kit Parker

Kevin Kit Parker (Harvard University)

24 September 2014. Biomedical engineers at Harvard University developed a model of human airway muscles on a miniaturized chip that emulates their actions during an asthma attack. The senior author of the paper describing the airway muscles chip, Kevin Kit Parker, is also a recipient of a new National Institutes of Health grant to develop a chip emulating cardiopulmonary systems, one of 11 awards announced yesterday to advance tissue-chip devices for drug screening.

The human airway muscles emulation chip is described in a recent issue of the journal Lab on a Chip (registration required), where Parker and colleagues built the model as a tool to better test asthma drugs, which often have limited success in human clinical trials. Among the problems facing asthma drugs in trials are the differences in respiratory anatomy between lab animals and humans, and the complex and variable nature of asthma, which makes it difficult to find a single drug that can treat the disease.

Asthma is chronic condition, where the airways become inflamed and narrow, causing people with asthma to experience wheezing, shortness of breath, tightness in the chest, and coughing for periods of time. Centers for Disease Control and Prevention estimates that in 2010 some 18.7 million adults had asthma, along with 7 million children.

The chip is made of engineered smooth bronchial muscle tissue in an elastomer-polymer material, arrayed in layers on a glass surface to simulate construction of airways. The researchers submitted the airway chip to interleukin-13, a protein found in the airways of people with asthma.

The team then introduced acetylcholine, a neurotransmitter that signals muscles to contract, which caused the simulated airway muscles to rapidly tighten, as happens during an asthma attack. When exposed to drugs that cause muscles in the airway to relax — beta agonists and  muscarinic antagonists — such as those found in inhalers often used by people with asthma, the muscles on the chip relaxed. Tests with the chip also showed the researchers could calibrate muscle contractions on the chip by varying doses of the drugs.

In addition, the team looked into properties of cells in muscle tissue on the airway chip. The researchers found the presence of interleukin-13 causes a greater alignment of actin filaments, which help form the structure of cells, resulting in enlargement of smooth muscle cells, a characteristic of muscles in airways of people with asthma. The team exposed the airway chip to a drug known as HA-1077, a compound used to widen blood vessels by inhibiting smooth muscle contractions, which targets a cell signaling pathway addressing actin fibers.

Tests with HA-1077 show the drug, not currently used to treat asthma, makes tissues on the airway muscle chip less sensitive to signals that trigger muscle contractions associated with asthma. The researchers reported early evidence that the combination of HA-1077 and asthma drugs worked better with airway muscles on the chip than asthma drugs alone.

 NIH awards for tissue chip development

National Institutes of Health yesterday announced 11 recipients of grants to develop chip devices that emulate human organs and tissues that can eventually be linked together to simulate complex whole body functions. The program, led by the National Center for Advancing Translational Sciences (NCATS) in NIH, aims to provide alternatives to current methods to test drugs for safety and effectiveness. Funds for the first year of the three-year grants total $17 million.

Parker’s lab in Harvard’s School of Engineering and Applied Sciences was among the recipient’s of the NCATS grants. The award of nearly $1.2 million supports development of an integrated model of the human cardiopulmonary system. Among the reasons for failure of some drugs in late-stage clinical trials is toxicity to the heart, and the device to be developed aims to emulate human heart and lungs in both healthy and diseased states to test drugs for toxicity before trials with humans.

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