Emergency Preparedness and Response

Organs-On-Chips for Radiation Countermeasures

Background | Project Description | Project Outcomes | Publications | Awards

FDA awards contract to Harvard University’s Wyss Institute for Biologically Inspired Engineering to test candidate radiation medical countermeasures, using novel organs-on-chips technology 
 
 Organ-on-a-chip held between thumb and forefinger (image courtesy Wyss Institute for Biologically Inspired Engineering)

Performer: Wyss Institute for Biologically Inspired Engineering disclaimer icon at Harvard University

Principal Investigator: Donald E. Ingber, MD, PhD

Project dates: August 2013 - August 2018

Background

The development of medical countermeasures to treat acute radiation syndrome (ARS) is a high-priority for the U.S. government. ARS is an illness affecting a combination of organs that occurs when the body receives a high dose of radiation – over a short period of time – as would be expected to occur after a nuclear or radiological incident. 

The development of medical countermeasures to treat ARS presents complex scientific challenges. For example, ARS may involve many organ systems, which makes it difficult to study candidate medical countermeasures that target the radiation effects on one specific organ system in animal models. In addition, certain candidate medical countermeasures cannot be effectively studied in animal models because their activity is specific to humans. 

Project Description

Harvard University’s Wyss Institute for Biologically Inspired Engineering is developing organs-on-chips that mimic the structure, function, and interactions between the living tissues within human organs – such as the lung or intestine – on chips the size of a thumb drive.
 
Under the contract, Wyss Institute scientists will develop models of radiation damage in their lung, gut, and bone marrow organs-on-chips and then use these models to test candidate medical countermeasures to treat such damage. This will provide a capability to evaluate candidate medical countermeasures for ARS within the specific context of a target human organ system, which may yield valuable information for facilitating development.

Project Outcomes

This project will:
  • Advance the development of microphysiological systems (organs-on-chips) that recapitulate many of the complicated interactions between cells and tissues that occur in the gastrointestinal tract, bone marrow, and lungs
  • Characterize how these organs-on-chips systems respond to radiation exposure and compare the responses against those known to occur in people and animals exposed to radiation
  • Link together the different organ-on-chips systems (for example, gut chip and bone marrow chip) and expose them to radiation to simulate the interplay between different organ systems exposed to radiation
  • Test candidate radiation medical countermeasures in the individual organs-on-chips and linked organ-on-chips systems
Publications
  • Huh D et al., Microfabrication of human organs-on-chips. Nature Protocols 8:2135-57, 2013 - full text (open access) disclaimer icon
  • Torisawa YS et al., Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro. Nature Methods 11:663-9, 2014 - full text (open access) disclaimer icon
  • Bhatia SN and Ingber DE., Microfluidic organs-on-chips. Nature Biotechnology 72, 201432:760-72, 2014 - full text (open acess) disclaimer icon
  • Esch EW, Bahinski A, Huh D, Organs-on-chips at the frontiers of drug discovery. Nature Reviews Drug Discovery. doi:10.1038/nrd4539, published online 20 March 2015 - abstract disclaimer icon - full text disclaimer icon
  • Kim HJ, Collins JJ, Ingber DE.  Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. PNAS. 15 Nov 2015 - abstract disclaimer icon - full text disclaimer icon
  • Kim HJ, Lee J, Choi JH, Bahinski, A, Ingber DE. Co-culture of Living Microbiome with Microengineered Human Intestinal Villi in a Gut-on-a-Chip Microfluidic Device. J. Vis. Exp. 2016 Aug 30 (114) – journal linkdisclaimer icon
Awards

 

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