Friday , May 14 2021

Tissue chips in space light on human health



A small device that contains 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 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 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 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 shreds in space to appear much like an astronaut's body and experience the same rapid change."

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 known as 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 tissue types. And it must have microfluidic channels, because every tissue in the body has vasculature to take in blood and nutrients and remove detritus."

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.

"Essentially, you get a functional unit of what human tissues are, outside the body," says Low. "It's like taking a little bit of you, put it in a pot and watch 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 to develop new drugs. About 30% of promising drugs have been found to be toxic in human clinical trials despite positive preclinical studies in animal models. About 60% 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 in the drug development process to have better models for predicting the responses to the human body and to measure the toxicity much earlier in the process as well as to make sure that a potential drug actually does what it's intended to be without negative side effects, says 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 effectively than current methods.

Tissue Chips in Space is based on microfluidic knowledge gained in previous space investigations, Warren said, but also required to create new, not yet tested hardware and systems.

First, the system must be automated as much as possible.

"We would simplify everything for space flight, so astronauts just need to plug in a box at the space station, without doing anything with syringes or liquids," she says.

The engineers also got miniaturized complexes, large equipment used to maintain appropriate environmental conditions for the chips. The hardware, the size of a refrigerator in 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 fly, but special mechanisms are needed to remove them in microgravity.

Automation and miniaturization made for Tissues Chips in Space contributes to standardization of tissue technology, which also deepens research on the ground.

"Now we have a tool that can be sent anywhere on the planet," says Low.

On Earth, researchers work together 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.

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

In addition, another four projects are planned for launch in the summer of 2020, including two on cardiac cardiovascular technology to understand cardiovascular health, one on muscle waste and another for intestinal inflammation.

In the end, Warren says that technology could give astronauts space to bring personal chips that can be used to monitor changes in their bodies and to test possible countermeasures and therapies.

Image: Made of flexible plastic, tissue chips have gates and channels to provide nutrients and oxygen to the cells inside them.
Credits: NASA


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