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July 17, 2018

Organs-on-Chips Take Flight

Initiative to Use Technology Aboard International Space Station Set to Begin

Organs-on-Chips Take Flight

Mongolian gerbil [Alastair Rae is licensed under CC BY 2.0

  • Organs-on-chips technology are about to take flight, literally. The National Center for Advancing Translational Sciences and the Center for the Advancement of Science in Space co-granted funding last year to launch five research teams’ chips into space. The projects will be shuttled over the span of two launches, the first in November and the next in February.

    “As far as I know, this is the first attempt to send organ-on-chip devices up to space,” says Dongeun (Dan) Huh, Ph.D., bioengineer at the University of Pennsylvania and co-lead for one of the projects. He is also one of the pioneers of the organs-on-chips technology

    The five projects selected are from both academic and commercial U.S. groups and are part of a four-year initiative to use organs-on-chips technology aboard the International Space Station (ISS) National Laboratory. Current funding covers the first two years, or phase one, of the project, which includes the launches planned for November and February. The subsequent two years of funding, phase two, will be granted if funds are available and milestones met. Although conducted in space, most of the research projects are expected to yield findings that apply not only to astronaut health but also to health on Earth.

    “The strength of all these humans organs-on-chips, on Earth as well as hopefully in space, is they have much more fidelity to what you would expect for cellular function actually inside, let’s say, a human kidney,” says Jonathan Himmelfarb, M.D., professor of medicine at the University of Washington and co-lead for one of the projects. “It’s a challenge with all in vitro systems that are examining cell biology to assume that a cell outside the body behaves the same way as a cell inside an organ.”

  • From Immunosuppression to Age Reversal

    The five projects selected for funding cover a swath of diseases and organ-on-chip systems. The project Dr. Huh is a part of uses two chips, one that mimics the airway and another that mimics bone marrow, to investigate immunosuppression in astronauts.

    “It’s been known since the early days of space flight that the astronauts somehow become more susceptible to infection or inflammation during or right after space flight,” says Dr. Huh. “Bone marrow is very important in immune function because the bone marrow is where white blood cells are made. When there’s infection happening in the body, the white blood cells are released, or mobilized, from the bone marrow and they travel to the infected tissue and organs, and they try to resolve the infection.”

    Once in space, the chips will be infected separately with pathogens and culture medium continuously collected for later analysis back on earth.

    “At the end of the experiments, we’re going to fix the cells, so we can preserve the tissue,” he says. “When the devices return back to earth, we can further process these samples to really find out what has happened up in space.”

    For phase two of the project, the airway-on-a-chip and bone-marrow-on-a-chip will be connected to form an integrated system that more closely mimics reality. The airway tissue will be then infected to see how the process of the immune cell mobilization from the bone marrow and subsequent recruitment to the infected airway tissue happens.

    A research team from Massachusetts Institute of Technology (MIT) is launching their joint-on-a-chip made of human cartilage, bone, and synovium to study post-traumatic osteoarthritis in microgravity. Because this disease occurs on Earth as well as in space, the researcher will simultaneously study their joint-on-a-chip on Earth too.

    For phase two of the project, Murat Cirit, Ph.D., director of The Translational Center of Tissue Chip Technologies at MIT and co-lead on the project, says they will test five or six drugs on the disease model in space and on Earth. The goal will be to determine the best drug treatment for post-traumatic osteoarthritis.

    Dr. Himmelfarb is co-leading the project to study how microgravity affects kidney tubular function.

    “Astronauts can develop kidney-related health problems in a microgravity environment,” says Dr. Himmelfarb. “They have a high risk of getting kidney stones, which can be a mission critical emergency.”

    In addition to kidney stones, kidney dysfunction can influence the degree of proteinuria, which is abnormally high protein levels in the urine, and also plays a role in osteoporosis.

    The first phase of the project involves launching two proximal-tubule-on-a-chip disease models, one for proteinuria and the other for vitamin D activation. The researchers are studying vitamin D activation because the proximal tubule in the kidneys converts vitamin D to its active form, calcitriol, and vitamin D is essential for bone health and preventing osteoporosis.

    “We have been studying vitamin D trafficking and metabolism in our proximal-tubule-on-a-chip and it occurred to us that in space, without gravitational cues, the proximal tubule cells may not polarize the right way and they may not traffic the vitamin D into the cell the right way to make the active form of vitamin D,” explain Dr. Himmelfarb. “If that’s the case, then perhaps the astronauts should receive calcitriol rather than [vitamin D] to prevent osteoporosis in space.”

    For phase two, the researchers will build a distal-tubule-on-a-chip to study kidney stone crystallization.

    These experiments will require some hands-on participation from the astronauts in the ISS, so the team is creating procedure manuals that have very specific instructions and are tailored to the ISS environment so that the experiments are conducted in a rigorous way.

    “That’s an exciting and challenging piece of this,” says Dr. Himmelfarb.

    Emulate, Inc., a private company that is developing organs-on-chips technology, is launching their blood-brain-barrier-on-a-chip to study human brain health in microgravity. Astronauts who spend a long time in space often return with vision problems, and a small study last year showed changes in astronauts’ brain structures, further warranting study of brain health in space.

    Geraldine Hamilton, Ph.D., president and CSO of Emulate, explains that the brain chip will be used to study how other space travel stressors, such as hypergravity experienced during launch, hypoxia, and increased levels of stress hormones, influence brain function. However, astronauts are not the only ones slated to benefit.

    “An important secondary purpose of the project is to provide insights into the relationship between inflammation and brain function, a very active area of investigation for furthering understanding of neurodegenerative diseases on Earth, such as Alzheimer’s and Parkinson’s disease,” says Dr. Hamilton.

    The fifth project centers on the fact that the bodies of astronauts in space, as well as older people on Earth, have difficulty repairing after injury. The reason for this may be an aging immune system, so researchers from the University of California, San Francisco (UCSF) are launching two stem-cell-based chips to study the immune system as it declines with age. Microgravity is a good model because it accelerates aging.  

    “The overall goal is we wanted to study the immunobiology of immune cells in space,” says Sonja Schrepfer, M.D., Ph.D., associate professor of surgery at UCSF and investigator on the project. “Then we wanted to see how the immune cells, which are altered in space, will affect the stem cells in the body.”

    When selecting which stem cells to use on chips, she says, “I had to limit it to two different stem cell types.” The types chosen were mesenchymal stem cells, which help wounds heal, and endothelial progenitor cells, which help regenerate vascular tissue. The chips also contain immune cells.

    For the first phase of the project, the goal is to show that immune cells are aging in space and that this probably will affect the stem cells, she says. The second phase of the project will focus on whether it is possible to reverse aging of the immune system.

    “This is the part we are really excited about,” she says about the second phase. If they see reversible aging with their chip, “we could start thinking about how we reverse that here on Earth for our patients.”

  • Going Hands Free

    Some of the research groups are devising increasingly hands-free systems to minimize manual input from astronauts on the ISS.

    “Experiments in space require very robust functionality. Systems must be very small, extremely reliable, completely integrated, remote controlled, and totally automated,” explains Dr. Hamilton. Emulate has a fully automated system that can be remotely controlled from Earth. “These requirements obviously have great value for terrestrial instrumentation as well.”

    Each research group has at least one implementation partner to help execute the project. Dr. Huh says one of theirs, SpacePharma, has a box-like automated system in which they can place their organs-on-chips devices. Thus, the research team is designing their devices to be compatible with this automated system. “Because the box system has objectives that can visualize the cells, we would be monitoring the infection in the airway-on-a-chip devices close to real-time from the Earth,” explains Dr. Huh.

    The MIT team is designing a nearly hands-free system. “We are working right now with our implementation partner to build hardware we can run in the International Space Station with minimal crew time,” says Dr. Cirit.

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