Organ-on-a-chip Models Human Disease
November 8, 2012

Animal Testing Could Eventually Be Replaced With Organ-on-a-chip

[ Watch the Video: Researchers Create Human Breathing Lung-On-A-Chip ]

Connie K. Ho for — Your Universe Online

Researchers from Harvard University´s Wyss Institute for Biologically Inspired Engineering recently revealed that they have developed a “lung-on-a-chip” that mimics human diseases and could be the next step forward in terms of research.

With the study, the scientists believe that the organ-on-a-chip could eventually take the place of animal testing. They were able to observe drug toxicity and determined possible new therapies that could limit certain medical conditions from developing. The chip emulates pulmonary edema in a microchip and is surrounded by living human cells. The findings, published in the journal Science Translation Medicine, show that this kind of technology could eventually take the place of traditional research methods on drug development.

"Major pharmaceutical companies spend a lot of time and a huge amount of money on cell cultures and animal testing to develop new drugs," remarked the study´s senior author Dr. Donald Ingber, the founding director of the Wyss Institute, in a prepared statement. “But these methods often fail to predict the effects of these agents when they reach humans."

Crystal clear and made up of flexible polymer, the lung-on-a-chip device is as small as a memory stick and two of the channels in the device are split by a flexible, thin, porous membrane with human lung cells on one side and human capillary blood cells on the other. The human lung cells are taken from the air sac and have exposure to air, while the human capillary blood cells have a medium that flows over the surface. To re-create the ability of human lungs to expand and extract, the scientists added a vacuum on the side channels.

The researchers began by studying interleukin-2 (IL-2), a cancer chemotherapy drug. One side effect of the drug was pulmonary edema, which caused the lungs to fill with blood clots and fluid. The scientists discovered that, when an injection of IL-2 was sent into the blood channel of the lung-on-a-chip, fluid then moved across the membrane and the two tissue layers; this led to a decrease in the volume of air in the channel and made it difficult to move oxygen from one place to another. However, when the team of investigators used the vacuum connected to the chip to initiate breathing, it elevated the fluid leakage over three times more.

Based on the findings, researchers believe that doctors who treat patients on a respirator with IL-2 should decrease the tidal volume of air pushed into the lungs to lower the adverse effects of the drug.

"Organs-on-a-chip represents a new approach to model the structure, biology, and function of human organs, as evidenced by the complex breathing action of this engineered lung. This breathing action was key to providing new insight into the etiology of pulmonary edema," explained Dr. James M. Anderson, director of the NIH Division of Program Coordination, Planning, and Strategic Initiatives, in the statement. "These results provide support for the broader use of such microsystems in studying disease pathology and hopefully for identifying new therapeutic targets."

Furthermore, the researchers believe that pulmonary edema symptoms found in the lung-on-a-chip disease could be reduced by treating the tissues with a transient receptor potential vanilloid 4 (TRPV4) channel blocker. Another study published in the Science Translation Medicine stated that the benefits of TRPV4 in lowering pulmonary edema were also seen in the results of animal models that had pulmonary edema due to heart failure.

"In just a little more than two years, we've gone from unveiling the initial design of the lung-on-a-chip to demonstrating its potential to model a complex human disease, which we believe provides a glimpse of what drug discovery and development might look like in the future," concluded Ingber in the statement.