Organ-on-a-Chip Simulates Asthmatic Airway

UPDATED: Oct. 7, 2014, at 2:59 a.m.

Scientists at Harvard’s Wyss Institute for Biologically Inspired Engineering have developed a new chip that mimics the function of an asthmatic airway and has the potential to speed up the drug-testing process.

Testing a drug often costs more than a billion dollars and has traditionally consisted of a two-part process—the pre-clinical phase of testing on animals and the clinical trial of testing on humans. While many drugs pass through the first phase, they fail when they reach the clinical phase, a crucial component of pharmaceutical research, according to A. Peyton Nesmith, a research assistant at SEAS and the lead author of a paper published in August about the chip.

“You’ve got to test drugs on humans because testing on rats or other animals that are not humans or primates is not sufficient to test the safety of the drug or to test the efficacy—that is, how effective it is at curing a disease,” said Kevin Kit Parker, a bioengineering and applied physics professor at the School of Engineering and Applied Sciences, who leads the team of scientists at the Wyss Institute.

The scientists at the Wyss Institute may have found a way to eliminate this problem through micro-scale models, the latest of which simulates an asthmatic airway. Each organ-on-a-chip that the team has engineered mimics the function of a human body part on a controlled, small-scale level.

“The idea is that we want to build every organ system—the heart, the lungs, the airway, the liver, all the adrenal organs, and then link them up to hopefully stimulate normal human physiology,” Nesmith said. Nesmith built a model of a normal airway and then triggered asthma in that airway by using human cells and focusing on muscular structure.

“Peyton did something very smart in that he realized that he could get healthy cells from a company, and he could induce the asthmatic phenotype in those cells,” Parker said.

To build the chip, Nesmith assembled very thin glass, polymer, and cell culture layers. Using this process, the team has experimented with different types of cells—including heart, vascular and bronchial cells—and has created organs-on-a-chip since 2003.

“The biggest challenge for organs-on-chips in general is that they need to be consistent,” said Megan L. McCain, a biomedical engineering professor at the University of Southern California who worked on the Wyss Institute’s heart-on-a-chip project.

Researchers must also consider the implications of how working with tiny pieces of engineered tissues rather than full-sized human models might affect how to scale drug dosages, McCain said.

The organ-on-a-chip models involves collaboration across disciplines such as engineering, applied mechanics, and biology.

“When you take a look at a project like this, it’s kind of uniquely Harvard,” Parker said. “A lot of the times to be on the cutting edge, you take things that don’t belong together, and you put them together.”