ABERDEEN PROVING GROUND, Md. -- The U.S. Army Edgewood Chemical Biological Center welcomed researcher Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine and chairman of the Department of Urology at Wake Forest University, who gave a lecture to a gathering of ECBC scientists Nov. 9.
Atala, who is a surgeon and a scientist, has gained international prominence for his research in using healthy human cells to regenerate diseased or damaged tissue and organs, and is a featured speaker at TED Conferences. He came to APG to meet with the team from ECBC that is working with him on a project called ECHO (Ex Vivo Console of Human Organoids).
The ECBC team is working on the development of what is being referred to as a "human on a chip" that will be used to model the body's response to chemical and biological agents and develop potential treatments.
"Our mission is to assess threat agent compounds in a human model, especially as we identify a new threat agent," said Dr. Robert Kristovich, chief of the Molecular Toxicology Branch at ECBC, whose team of eight scientists are working on the project. "This method provides more rapid and more robust results." This is the fourth year of ECHO.
Atala's team at Wake Forest is leading the research effort through a cooperative research and development agreement with ECBC. Other partners include the Defense Threat Reduction Agency, which provided $24 million in funding for the project; Harvard University; Johns Hopkins University; Morgan State University; and the University of Michigan.
"ECBC has been a wonderful partner in this venture," Atala said.
They are developing organoids for assessing the toxicity of threat agent compounds with a goal of minimizing or replacing animal testing, Kristovich said. Organoids are little clusters of human cells that mimic the function of an actual organ in the body, he said. They're focusing on four organoids: liver, heart, lung and vascular (blood vessels).
All functions of each organ have been put on a 300 micron spheroid that's then placed in a Petri dish. The organoids are put on a chip in shared media all connected by microfluidics that simulates blood flow. Then, scientists look at how they affect each other.
"We're looking at how the organs communicate with each other, how they metabolize and influence each other," Kristovich said. "For example, does the liver organoid make it more toxic to the heart?"
In his talk, Atala said the "human on a chip" provides real-time biosensing of physical and chemical sensors such as temperature, heart rate, oxygen and PH levels. On-chip electrochemical biomarkers allow for detection to be performed every 10 minutes.
If successful, the "human on a chip" technology would eliminate use of animals in testing. "It's imperative that we find alternatives to animal testing," said Dr. Harry Salem, chief scientist for Life Sciences at ECBC and one of the researchers on the team.
After Atala's presentation at ECBC, the team then traveled to the Food and Drug Administration headquarters in Washington to present the latest findings to FDA researchers. The presentation was given as part of a hot topics speaker series offered at the FDA. This was the third presentation, or progress report, on the ECHO project that the team has given to the FDA, Salem said.
Salem spoke on the difficulties of predicting human reaction from animals, while ECBC biologist Dr. Russ Dorsey gave a progress report on the ECHO project, and Atala gave a similar presentation to what he provided at ECBC.
"Researchers at the Food and Drug Administration are also wanting to know if these in vitro studies can predict a prolonged a QT wave, an indication of heart problems, which is crucial in determining harmful side effects of prescription drugs and can lead to the FDA taking a drug off the market," said Salem. "That's the future of medicine."
Atala and his team of experts at the Wake Forest Institute for Regenerative Medicine have been experimenting with culturing 3D human tissue on a chip and 3D replacement organs since the early 1990s using a 3D printer specially designed by his team. But ECHO is one of the first efforts to combine several organs in the same device to model the human response to chemical toxins or biological agents.
"There are many challenges ahead -- funding, regulatory and more," Atala said, "but one thing is certain: they have the potential to make Soldiers' lives better."
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The U.S. Army Edgewood Chemical Biological Center is part of the U.S. Army Research, Development and Engineering Command, which has the mission to provide innovative research, development and engineering to produce capabilities that provide decisive overmatch to the Army against the complexities of the current and future operating environments in support of the joint warfighter and the nation. RDECOM is a major subordinate command of the U.S. Army Materiel Command.
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