Corporate Banner
Satellite Banner
Pharma Outsourcing
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Wyss Institute Models a Human Disease in an Organ-on-a-Chip

Published: Friday, November 09, 2012
Last Updated: Friday, November 09, 2012
Bookmark and Share
Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have mimicked pulmonary edema in a microchip lined by living human cells, as reported today in the journal Science Translation Medicine.

They used this "lung-on-a-chip" to study drug toxicity and identify potential new therapies to prevent this life-threatening condition.

The study offers further proof-of-concept that human "organs-on-chips" hold tremendous potential to replace traditional approaches to drug discovery and 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," says Donald Ingber, M.D., Ph.D., founding director of the Wyss Institute and senior author of the study, "but these methods often fail to predict the effects of these agents when they reach humans."

The lung-on-a-chip device, which the team first described only two years ago, is a crystal clear, flexible polymer about the size of a memory stick that contains hollow channels fabricated using computer microchip manufacturing techniques. Two of the channels are separated by a thin, flexible, porous membrane that on one side is lined with human lung cells from the air sac and exposed to air; human capillary blood cells are placed on the other side with medium flowing over their surface. A vacuum applied to side channels deforms this tissue-tissue interface to re-create the way human lung tissues physically expand and retract when breathing.

Wyss Technology Development Fellow Dongeun Huh, Ph.D., who also holds appointments at Boston Children's Hospital and Harvard Medical School, studied a cancer chemotherapy drug called interleukin-2 -- or IL-2 for short -- in the lung-on-a-chip. A major toxic side effect of IL-2 is pulmonary edema, which is a deadly condition in which the lungs fill with fluid and blood clots.

When IL-2 was injected into the blood channel of the lung-on-a-chip, fluid leaked across the membrane and two tissue layers, reducing the volume of air in the other channel and compromising oxygen transport -- just as it does in lungs of human patients when it is administered at the equivalent doses and over the same time course. Blood plasma proteins also crossed into the air channel, leading to the formation of blood clots in the air space, as they do in humans treated with IL-2.

But one result came as a surprise.

It turns out the physical act of breathing greatly enhances the effects of IL-2 in pulmonary edema -- "something that clinicians and scientists never suspected before," Ingber says. When the team turned on the vacuum attached to the chip to simulate breathing, it increased fluid leakage more than three-fold when treated with the clinically relevant IL-2 dose, and the Wyss team confirmed that the same response occurs in an animal model of pulmonary edema. This result could suggest that doctors treating patients on a respirator with IL-2 should reduce the tidal volume of air being pushed into the lungs, for example, in order to minimize the negative side effects of this drug.

Most exciting for the future of drug testing was the Wyss team's finding that "this on-chip model of human pulmonary edema can be used to identify new potential therapeutic agents in vitro," Ingber says. The pulmonary edema symptoms in the lung-on-a-chip disease model could be prevented by treating the tissues with a new class of drug, a transient receptor potential vanilloid 4 (TRPV4) channel blocker, under development by GlaxoSmithKline (GSK). In a separate study published by the GSK team in the same issue of Science Translation Medicine, the beneficial effects of TRPV4 inhibition in reducing pulmonary edema were independently validated using animal models of pulmonary edema caused by 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," Ingber says.

The cross-disciplinary, multi-institutional team that was led by Ingber and Huh also included Wyss Postdoctoral Fellow Daniel Leslie, Ph.D.; Benjamin Matthews, M.D., assistant professor of pediatrics in the Vascular Biology Program at Boston Children's Hospital and Harvard Medical School; Wyss Institute Researcher Jacob Fraser; Samuel Jurek, a researcher at Boston Children's Hospital and Harvard Medical School; Senior Wyss Staff Scientist Geraldine Hamilton, Ph.D.; and Senior Scientific Investigator Kevin Thorneloe, Ph.D., and Investigator M. Allen McAlexander from GlaxoSmithKline. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at Harvard School of Engineering and Applied Sciences.

"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," said Dr. James M. Anderson, M.D., Ph.D., director of the NIH Division of Program Coordination, Planning, and Strategic Initiatives that provided partial support for this research through the Common Fund's Regulatory Science program. "These results provide support for the broader use of such microsystems in studying disease pathology and hopefully for identifying new therapeutic targets."


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Experimental MERS Vaccine Shows Promise in Animal Studies
A two-step regimen of experimental vaccines against Middle East respiratory syndrome (MERS) prompted immune responses in mice and rhesus macaques, report National Institutes of Health scientists who designed the vaccines.
Young South African Women can Adhere to Daily PrEP Regimen as HIV Prevention
NIH-funded study finds men in Bangkok, Harlem also successful in taking daily dose.
Researchers Find Key Player in Diabetic Kidney Disease Through Power of Metabolomics
Discovery could lead to new and better diagnostic marker for chronic kidney disease.
Immunotherapy Shows Promise for Myeloma
A strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
Santhera Announces First Patient Dosing with Omigapil in CMD
Company announces full patient recruitment of CALLISTO study.
Study Shows Promise of Precision Medicine for Most Common Type of Lymphoma
The study appeared online July 20, 2015, in Nature Medicine.
HIV Control Through Treatment Durably Prevents Heterosexual Transmission of Virus
NIH-funded trial proves suppressive antiretroviral therapy for HIV-infected people effective in protecting uninfected partners.
Adaptimmune's Novel Cancer Therapeutics Show Positive Clinical Trial Results
The company has announced that positive data from its Phase I/II study of its affinity enhanced T-cell receptor (TCR) therapeutic targeting the NY-ESO-1 cancer antigen in patients with multiple myeloma has been published.
Early Antiretroviral Therapy Prevents Non-AIDS Outcomes in HIV-infected People
NIH-supported findings illustrate manifold benefit of therapy.
Adaptimmune’s NY-ESO-1 TCR-engineered T-Cells Demonstrate Durable Persistence
Study has been published in Nature Medicine.
Scroll Up
Scroll Down
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!