A Harvard University team created a human airway "muscle-on-a-chip" that could be used to test new asthma drugs, leading to better treatments for the common condition.
Asthma drugs have barely improved over the past 50 years, even though the disease affects almost 25 million people in the United States alone. Asthma is characterized by symptoms such as coughing, wheezing, and trouble breathing.
"Every year asthma costs many tens of billions of dollars, significant productivity due to lost work and school days, and even lives," said senior author Kevin Kit Parker, Tarr Family Professor of Bioengineering and Applied Physics at the Harvard School of Engineering and Applied Sciences (SEAS) and a Core Faculty member at Harvard's Wyss Institute for Biologically Inspired Engineering. "We were thrilled with how well the chip recapitulated the functioning of the human airway."
This new device perfectly mimics the way smooth muscles in human airways contract, both under normal conditions and when exposed to asthma triggers. The chip is made of a soft polymer that is mounted on a glass substrate and contains a planar array of microscale engineered human airway muscles.
To mimic an asthmatic allergic response the researchers introduced interleukin-13 (IL-13), which is a natural protein commonly found in the airway of asthmatic patients. The protein is believed to help regulate allergic reactions in the soft muscle. They also exposed the chip to acetylcholine, a neurotransmitter that causes contractions in the smooth muscle. When introduced to these factors the artificial muscle hypercontracted, causing the soft material to curl up.
The researchers also achieved the reverse effect by administering the drug β-agonists, which is used in inhalers; once the chip was exposed to the common drug the artificial muscles relaxed. The team was able to measure the contractile stress of the muscle tissue when exposed to different levels of the drug.
"Our chip offers a simple, reliable and direct way to measure human responses to an asthma trigger," said lead author Alexander Peyton Nesmith, a Ph.D./M.D. student at Harvard SEAS and the University of Alabama at Birmingham.
The chip allowed researchers to find smooth muscle grew larger when exposed to IL-13 over time. They also observed an increased alignment of actin fibers, super-thin cellular components that aid in muscle contractions.
The researchers looked at how IL-13 changes the expression of the contractile protein called RhoA by introducing a drug called HA1077, that is not currently used to treat asthma patients. The drug proved to make asthmatic tissue on the chip less reactive to asthma triggers. The drug could one day be used in combination therapies to help improve asthma treatment.
"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," said Donald Ingber, who is the founding director of the Wyss Institute, Judah Folkman Professor of Vascular Biology at Harvard Medical School and Children's Hospital Boston and Professor of Bioengineering at Harvard SEAS. "The airway muscle-on-a-chip provides an important and exciting new tool for discovering new therapeutic agents."
The work was funded by the National Institutes of Health and Harvard SEAS and was published in a recent edition of the journal Lab on a Chip.
