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A small device containing human cells in a 3D matrix represents a considerable advance in the ability of scientists to test the response of these cells to stress, drugs and genetic modifications. The size of a USB key, these devices are called chips of tissue or organs on chips.
A series of investigations to test microgravity tissue fragments aboard the International Space Station is planned as part of a collaboration between the National Center for the Advancement of Translational Sciences (NCATS). National Institutes of Health (NIH) and Center for the Advancement of Sciences in Space. (CASIS) in partnership with NASA. The Tissue Chips in Space initiative aims to better understand the role of microgravity on human health and disease and to translate that understanding into an improvement in human health on Earth.
"Spaceflight causes many significant changes in the human body," said Liz Warren, CASIS Associate Scientist. "We expect the fabric chips in the space to behave much like the body of an astronaut and undergo the same kind of quick change."
Many changes in the human body caused by microgravity resemble the onset and progression of diseases associated with aging on Earth, such as bone and muscle loss. But space-related changes occur much more quickly. This means that scientists may be able to use fabric fragments in space to model changes that could take months or even years on Earth.
Also called micro-physiological system, a tissue chip needs three main properties, according to Lucie Low, NCATS Program Manager. "It must be in 3D, because humans are in 3D," she said. "It has to have multiple types of cells, because an organ is made up of all types of tissue, and it must also have microfluidic channels, because every tissue in your body has a vascular system to bring blood and nutrients and detritus. "
"The fabric chips give the cells a home," Warren said. 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 tissue is, outside the body," Low said. "It's like taking a little bit of yourself, putting it in a pot and looking at how your cells react to different stresses, different drugs, different genes and using it to predict what they would do in your body.
The development of new drugs is a potential application of tissue chips. About 30% of promising drugs have been shown to be toxic in human clinical trials despite favorable preclinical studies in animal models. About 60% of potential drug candidates fail for lack of effectiveness, which means that the drug does not have the desired effect on a person.
"It is necessary in the drug development process to have better models for predicting human body reactions and for assessing toxicity much earlier in the process, as well as to verify that a potential drug is doing what it is." 39 it's supposed to do without any unwanted side effects, "said 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 for predicting whether a drug, vaccine or agent Biological candidate is safer and effective in humans than current methods.
Tissue Chips in Space builds on microfluidics knowledge gained from previous space station investigations, Warren said, but it also required the creation of new hardware and systems that have not been tested yet. On the one hand, the system had to be automated as much as possible.
"We wanted to make it all simpler for spaceflight, so astronauts need to plug a box into the space station, without doing anything concrete with syringes or fluids," she said. Engineers also had to miniaturize the large, complex equipment used to maintain the proper environmental conditions for the chips. This equipment, the size of a refrigerator in the laboratories of the Earth, occupies about as much space as a shoebox in space.
Microfluidics presented unique challenges, such as the management of bubble formation. On Earth, bubbles float at the top of a fluid and escape, but special mechanisms are needed to eliminate them in microgravity.
The automation and miniaturization of tissue chips in space is contributing to the standardization of tissue chip technology, which is also advancing research on Earth. "We now have a tool that can be sent anywhere on the planet," Low said.
On Earth, scientists are working to link several organ chips to mimic the entire body. This could allow for precision medicine, or personalized disease treatment and prevention that takes into account the genes, the environment and the body of an individual.
This first phase of Tissue Chips in Space includes five surveys. A survey on the aging of the immune system is planned for the launch of the SpaceX CRS-16 flight, scheduled for mid-November. The other four, scheduled for launch on SpaceX CRS-17 or later flights, focus on lung host defense, the blood-brain barrier, musculoskeletal diseases and kidney function. These first flights test the effects of microgravity on fabric chips and demonstrate the capabilities of the automated system.
Approximately 18 months later, the five surveys conduct a second flight to further demonstrate the functional use of the model, for example by testing potential drugs on the affected organs. In addition, four more projects are expected to be launched in the summer of 2020, including two on artificial heart tissue to understand cardiovascular health, one on muscle wasting and another on intestinal inflammation.
In the end, said Warren, this technology could allow astronauts traveling into space to carry custom chips that can be used to monitor changes in their body and to test against possible -measures and therapies. This would be a big step forward to keep astronauts healthy during missions in deep space.
Related Links
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