It sounds like a Star Trek or Star Wars episode: NASA is sending organ chips into space - but that's the reality and has been since 2018. Despite all the justified criticism, space travel is booming, especially since SpaceX: More and more people are flying into space and the plans to permanently station people in space and send them on Mars missions have been openly communicated for some time. Organoids and multi-organ chips are now being used more frequently to study the effects the lack of gravity has on the human body.

The first earthly creature in space was - involuntarily - the dog Laika, who was rocketed into space by the Soviet Union in 1957. Seven hours later she died of overheating and stress; an extremely painful and long death. Many other animals such as dogs, monkeys and mice were brought into space in rockets in the following decades. The effects of weightlessness on the human body should be investigated. Nowadays, there are methods that are ethically appropriate and also reflect human biology much better than animal testing can. These engage human cells, which are also often developed into mini-organs, so-called organoids. These form organ-typical cell types and show properties which are similar to their “originals”. The mini-organs can also be connected within multi-organ chips, creating a kind of circulatory system with organoids. As this functions like a copy of the human body, they are often referred to as microphysiological systems (MPS) or simply "chips". They can then be used to research basic properties and functions as well as reactions, e.g. to drugs or chemicals. If a person's cells are used for this purpose, a patient-on-a-chip can be generated. These methods have opened up great opportunities in personalized medicine.

Space: endless challenges

Such methods that work with human material can excellently also be used in space research. In a space station, the body is exposed to a completely different and artificial environment - in a state that does not exist on Earth: zero gravity. The lack of gravity has many more and serious consequences for the organism than just floating around: muscles deteriorate, as do bones. Astronauts therefore need to exercise daily to maintain their functionality. There are also changes in the immune and circulatory systems (1). People who fly into space are also exposed to cosmic radiation, which increases the likelihood of cancer or circulatory disease and can cause acute radiation syndrome (ARS). "Animal models" routinely used to assess the effects of radiation cannot mimic the effects observed in humans (2).

Weightless scientific projects

International Space Station (ISS) 

In 2016, US government agencies (CASIS*, now ISS National Lab, and NCATS* of NIH*) therefore initiated the Tissue Chip for Drug Screening program. This involves sending tissue chips into space to the ISS* to better understand the effects of microgravity on human health and disease. These findings are intended to help improve health on Earth (3,4).

In 2017, five two-year grants totalling about $6 million USD were awarded to use tissue chip technology for translational research on board the ISS. In addition, about $8 million for in-kind support was provided. In 2018, four new grants totalling about $5 million were awarded to use the technology to study disease mechanisms and the efficacy of potential treatments in space. This research aimed to evaluate biomarkers, bioavailability, efficacy and toxicity of therapeutic agents before starting clinical trials. In the first phase of the initiative, tissue chips were developed and tested on the ISS. In the second phase, the functional applications of these models were refined to realize more specific experiments. Tissue chip developers are collaborating with ISS space specialists on the project to meet NASA qualification requirements and conduct pre- and post-flight analyses. In December 2018, the first NIH-supported tissue chips were launched into space. Four more projects followed in May 2019, replicating lung and bone marrow, bone and cartilage, the kidney, and the blood-brain barrier. In March 2020, projects on intestinal and heart tissue flew to the ISS. In December 2020, three more projects travelled to the ISS, including focusing on prevention of osteoarthritis after joint injuries. Two projects in May 2019 had their second flight in 2021, and another two projects followed in July 2022 to investigate muscle degradation and immune aging and its regeneration potential (4).

Promising methods for the future of space travel

The latest projects concentrate on the production of stem cells in space. These are brought to the ISS in August 2024. One of them investigates whether human induced pluripotent stem cells (iSPCs) grow and divide faster in microgravity. The results could help the development of methods for future large-scale bioproduction of products derived from stem cells in space. This could lead to new treatment options for heart disease, neurodegenerative diseases and many other diseases. The second project aims to develop a novel bioreactor for the production of stem cells for use in space (5).

The implementation of these technologies makes sense in any case: animal experiments are not prospectively transferable not only on earth but also in space. Every living organism also reacts completely differently to the absence of gravity.

However, the findings not only help astronauts, but also "earthlings". It has been observed that the onset and progression of diseases can be accelerated during space flight. This provides new insights into disease mechanisms that normally only develop after a longer period of time. Among other things, aging processes such as the development and progression of osteoarthritis can be investigated (1).

Using iPSC technology, heart muscle cells were grown from human cells and experimented with in space. After returning to Earth, the cells from Earth and those that have spent a while in space can be compared. This makes it possible to determine how the absence of gravity affects heart cells.

Since astronauts lose around 20% of their muscle mass in two weeks of weightlessness, research into muscles is a priority for space travel. For comparison: on Earth, a person over the age of 35 loses 1-2% per year. Although intensive muscle training on special equipment is mandatory for every astronaut, even intensive training sessions cannot completely compensate for this muscle loss. Muscle biopsies were taken from younger and older subjects and integrated into a so-called CubeLab™ (6).

Essentially, this is an automatic mini-laboratory: the chip is installed in the box-shaped device and connected to a system that continuously releases nutrient solution for the tissues to keep them alive. Cameras are also connected that take pictures of the muscle samples on a regular basis. All of this is controlled by a pre-installed program. The experiment therefore runs autonomously and constantly collects data. At the same time, muscle samples from the same test subjects are treated on Earth according to the same protocol so that the results can be compared. In this experiment, genes were identified that are involved in protein modification, signal reception and metabolism and whose expression is altered in space. In particular, a down-regulation of genes that code for skeleton-specific structural proteins was found, which indicates impaired muscle development.

These chip systems can be equipped with various other tissues and organoids. However, they are not automatically free of animal testing, as they can also be equipped with animal cells. This is not very common, precisely because the use of human cells avoids species differences and research interest is focused on human-relevant results. The great potential of these chip systems can be deduced from the fact that they are flown to the ISS - every gram is precisely calculated and everything that is sent up on the rocket is carefully considered. Only the most promising technologies go to heaven - like the human-based chip systems.

27.08.2024
Julia Radzwill, biologist

 

 

References

1. Yau A. et al. Biosensor integrated tissue chips and their applications on Earth and in space. Biosensors and Bioelectronics 2023; 222:114820
2. Tavakol D.N. et al. Modeling and countering the effects of cosmic radiation using bioengineered human tissues. Biomaterials 2023; 301:122267
3. National Institutes of Health National Institutes of Health (NIH): NIH-funded tissue chips rocket to International Space Station, 4.12.2018 (accessed on 06.08.2024)
4. National Center for Advancing Translational Sciences Tissue Chips in Space (accessed on 06.08.2024)
5. ISS National Laboratory Next Mission to Space Station Will Launch a Variety of Biomedical and Physical Science Research (accessed on 06.08.2024)
6. Parafati M. et al. Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight. npj Microgravity 2023; 9(1):1–11