Tissue chips in space shed light on human health

A small device containing human cells in a 3D matrix represents a giant step in scientists' ability to test how these cells respond to stress, medicine and genetic changes.

About the size of a thumb drive, the devices are known as tissue chips or bodies on chips.

A series of studies to test tissue chips in microgravity onboard the International Space Station is planned through a collaboration between the National Center for Advancing Translational Sciences (NCATS) at the National Institutes for Health (NIH) and the Center for the Advancement of Science in Space (CASIS) in collaboration with NASA. The Tissue Chips in Space initiative tries to better understand the role of microgravity on human health and disease and to translate that concept into a better human health on earth.

"Space travel causes many significant changes in the human body," says Liz Warren, associate program scientist at CASIS. "We expect tissue chips in space to behave as the body of an astronaut, and experience the same kind of rapid change."

Many of the changes in the human body caused by microgravity are similar to the onset and progression of diseases associated with aging on earth, such as bone and muscle loss. But space-related changes occur much faster. This means that scientists may be able to use tissue chips in space to model changes that sometimes take months or years to happen on Earth.

Also called a micro-physiological system, a tissue chip needs three important properties, according to Lucie Low, scientific program manager at NCATS.

"It has to be 3D, because people are 3D," she explained. "It must have multiple, different types of cells, because an organ consists of all kinds of tissues, and it must have microfluidic channels, because every single tissue in your body has blood vessels to bring in blood and nutrients and remove waste."

Warren adds: "Tissue chips give cells a home away from home."

They mimic the complex biological functions of specific organs better than a standard 2D cell culture.

"In essence, you get a functional unit of how human tissues are, outside the body," Low says. "It's like taking a little bit of yourself, putting it in a jar and watching how your cells react to different stresses, different medications, different genetics and use that to predict what they would do in your body."

A possible application of tissue chips is the development of new drugs. Approximately 30% of promising drugs appear to be toxic in human clinical trials, despite favorable pre-clinical studies in animal models. Approximately 60% of potential drug candidates fail due to lack of efficacy, meaning that the drug does not have the intended effect on a person.

"There is a need in the development process of medicines to have better models to predict reactions of the human body and to measure toxicity much earlier in the process, as well as to check whether a possible drug actually does what it should do without harming side effects, "says Low.

As accurate models of the structure and function of human organs, such as the lungs, liver and heart, tissue chips provide researchers with a model to find a candidate drug, vaccine or biological agent more quickly and effectively than the current methods.

Tissue Chips in Space builds on microfluidics knowledge gained in previous space station research, says Warren, but also required new, untested hardware and systems.

To begin with, the system had to be automated as much as possible.

"We wanted to simplify everything for spaceflight, so that astronauts simply have to connect a box to the space station without having to deal with sprays or liquids," she says.

Engineers also had to miniaturize complex, large equipment that was used to maintain the correct environmental conditions for the chips. That hardware, the size of a refrigerator in laboratories on earth, costs about the same amount of space as a shoebox in space.

The microfluidics presented unique challenges, such as dealing with the formation of bubbles. On Earth, bubbles float to the top of a liquid and escape, but special mechanisms are needed to remove them in microgravity.

The automation and miniaturization carried out for Tissues Chips in Space contributes to the standardization of tissue chip technology, which also promotes research on the earth.

"Now we have a tool that can be shipped anywhere in the world," says Low.

On Earth, scientists are working on linking various organ chips to mimic the entire body. This can enable precision medicine, or adapted disease treatments and prevention that take into account a person's genes, environment and body.

The first phase of Tissue Chips in Space includes five studies.

An investigation into the aging of the immune system is planned for launch on the SpaceX CRS-16 flight, scheduled for mid-November.

The other four, planned for launch on SpaceX CRS-17 or subsequent flights, include defense of the lungs, the blood-brain barrier, musculoskeletal disease and kidney function. These first flights test the effects of microgravity on the tissue chips and demonstrate the power of the automated system.

All five studies make a second flight about 18 months later to demonstrate further functional use of the model, such as testing potential drugs on the specific organs.

In addition, four projects are planned for launch in the summer of 2020, including two on manipulated heart tissue to understand cardiovascular health, one on muscle wastage and one on intestinal inflammation.

Ultimately, says Warren, technology could allow astronauts to go into space to carry personalized chips that can be used to monitor changes in their bodies and to test possible countermeasures and therapies.

Depicted: made of flexible plastic, tissue chips have ports and channels to supply nutrients and oxygen to the cells in them.
Credits: NASA

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