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Small tissue chip in space a big step forward for research

A small unit containing human cells in a 3D matrix represents a huge step in the researchers' ability to test…

A small unit containing human cells in a 3D matrix represents a huge step in the researchers’ ability to test how these cells respond to stress, drugs and genetic changes. About the size of a thumb drive unit, the devices are known as tissue chips or bodies on chips.

A series of tests to test tissue chips in microgravity aboard the International Space Station are planned through collaboration between the National Center for Advancing Translational Science (NCATS) at the National Institutes for Health (NIH) and the Center for Space Science Advancement (CASIS) in collaboration with NASA. The Tissue Chips in Space initiative aims to better understand the microwave’s role in human health and disease and translate the understanding of improving human health on Earth.

“Spaceflight causes many significant changes in the human body,” said Liz Warren, associate program scientist at CASIS. “We expect tissue fractures in space to appear much like an astronaut’s body and experience the same kind of rapid changes.”

Many of the changes in the human body caused by microwaves resemble the appearance and progression of diseases associated with aging on the earth, such as bone and muscle loss. But space-related changes occur much faster. This means that researchers can use tissue chips in space to model changes that may take months or years to happen on Earth.

Also called a microphysiological system, a tissue chip needs three main features according to Lucie Low, NCAT’s Scientific Program Manager. “It must be 3D, because people are 3D,” she explained. “It must have several different types of cells, because a body consists of all types of tissues. And it must have microfluidic channels, because every tissue in the body has vessels to take in blood and nutrients and remove detritus.”

“Tissue chips give cells a home away from home,” said Warren. They mimic the complex biological functions of specific organs better than a standard 2D cell culture.

“Essentially, you get a functional unit of what human tissues are, outside the body,” says Low. “It’s like taking a little of you, putting it in a pot and watching how your cells respond to different stresses, different drugs, different genetics, and use it to predict what they would do in your body.”

A potential application of tissue chips is in the development of new drugs. About 30 percent of promising drugs have been found to be toxic in human clinical trials despite positive preclinical studies in animal models. About 60 percent of potential drug candidates fail due to lack of efficacy, which means that the drug does not have the intended effect on a person.

“There is a need to develop the process of developing better models to predict the responses of the human body and to measure toxicity a lot earlier in the process, as well as to make sure that a potential drug actually does what is meant to be without negative side effects, say Low. As exact models of human body structure and function, such as lung, liver and heart, tissue chip researchers provide a model to predict whether a candidate drug, vaccine or biological agent is safe in humans faster and more efficiently than current methods. 1

9659002] Tissue Chips in Space is based on microfluidics knowledge made in previous space investigations, Warren said, but also required to create new, not yet tested hardware and systems. For one thing, the system must be automated as much as possible.

“We would simplify everything for spaceflight, so astronauts need to basically just plug in a box at the space station, uta to do something easy with syringes or liquids, “she said. Engineers also got miniaturized complexes, large equipment used to maintain appropriate environmental conditions for the chips. The hardware, the size of a refrigerator in the laboratories on earth, takes up about as much space as a shox in space.

Microfluidics presented unique challenges, such as managing the formation of bubbles. On the ground bubbles flow to the top of a liquid and escape, but special mechanisms are needed to remove them in microgravity.

Automation and miniaturization performed for Tissue’s Chips in Space contributes to the standardization of tissue engineering, which further researches on Earth as well. “Now we have a tool that can be sent anywhere on the planet,” says Low.

On the ground, researchers are working to link multiple organ loops together to mimic the entire body. It can enable precision medicine or adapted disease treatments and preventive measures that take into account the individual’s genes, environment and body.

This first phase of tissue chips in space contains five studies. A survey of the immune system’s aging is scheduled for launch on the SpaceX CRS-16 flight, scheduled for mid-November. The other four, scheduled to start on SpaceX CRS-17 or subsequent flights, include lung defense, blood-brain barrier, musculoskeletal and kidney function. These first flights test the effects of microgravity on tissue chips and show the ability of the automated system.

All five surveys make a second flight 18 months later to further demonstrate functional use of the model, such as testing of potential drugs on the particular organs. In addition, four more projects are scheduled for launch in the summer of 2020, including two on manipulated cardiac tissue to understand cardiovascular health, one on muscle waste and another for intestinal inflammation.

In the end, Warren said that technology could allow astronauts to enter space to bring personal chips that could be used to monitor changes in their bodies and to test possible countermeasures and therapies. It would be a real step towards keeping the astronauts healthy on mission to deep space.

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