Cell culture techniques have helped researchers understand underlying genetic and regulatory networks within cells, but this reductionist approach has limits in capturing the complexity and connectivity of biological systems. The development and engineering of microphysiological systems (MPS), better known as “tissues-on-a-chip,” begins to incorporate complexity in an in vitro system that expands research capabilities and fills an important niche as a model system. These are 3D platforms engineered to support living human tissues and cells that accurately model the structure and function of human organs such as lungs, bone, skin, heart, and skeletal muscle and replicate the conditions in which cell growth takes place in the human body. Some chips are engineered with multiple tissue types with particular topology to test these inter-tissue interactions.  These chips are physiologically more accurate compared to monolayer 2D cultures, and can be used to perform experiments that would be inappropriate or difficult to study in whole animals or humans, for example pathogen inoculations and organ-to-organ signaling. In addition to propelling research discoveries, these novel platforms can facilitate drug screening, discovery, and testing for a range of human conditions. 

There are considerable efforts focused on expanding this technology in space. Not only do MPS pose advantages in biological research and pharmaceutical development, but the compact chip size and automation make them fitting tools on the space station. Furthermore, MPS can capture the physiological and cellular changes induced by microgravity, such as accelerated aging and immune dysfunction, which broadens the toolset that can be used to probe more mechanistic questions that will help us better understand biology, disease progression or drug effects. Below is a selection of space projects that use MPS in conjunction with the microgravity platform.

Immune dysfunction and infection

Microgravity induces immunosenescence, which increases the infectivity and virulence of pathogens. In order to test immune responses to pathogen infection, researchers are creating tissue chips that model the human airway by co-culturing lung tissue with bone marrow that produces immune cells. Following infection of lung tissue with a pathogen, researches will be able to study the lung response to the infection, whether lung tissue can effectively signal and mobilize bone marrow, and whether immune cells are activated and properly differentiated to combat infection.  

Stress, inflammation and the gut

Microgravity induces significant stress and inflammation, which can negatively impact the gastrointestinal tract. Researchers are using a “gut-on-a-chip” to model an innervated intestine and study the interaction between enteric physiology, stress, and immune response in microgravity. This human innervated Intestine-Chip (hiIC) co-cultures colonic epithelial cells, lamina propria-derived resident immune cells, and sensory neurons, which are then infected with pathogens to induce stress and inflammation. These chips can be automatically sampled and imaged on the space station on a daily basis and monitored in real time on Earth. Changes in the immune response and interactions with the intestinal cells could uncover novel mechanisms that trigger diseases of the intestine and serve as a platform to test potential therapeutic drugs. 

Inflammation and the blood-brain-barrier

Brain-Chips are being sent to space to test the interaction of inflammation induced by spaceflight and brain tissue. These chips consist of vascular endothelial cells which serve as a model of the blood-brain barrier and co-cultured with living neurons. These studies could uncover novel mechanisms relevant to neurodegenerative diseases such as Alzheimer’s and Parkinson’s, which are impacted by inflammation.

Immune Dysfunction and Regeneration

Immune dysfunction is involved in various aspects of injury and regeneration of various tissues. Researchers are testing whether microgravity alters the differentiation of a specific type of immune cell (CD8+ effector memory T cells, TEMRA cells), and how the immune cells subsequently impact the ability of progenitor cells to regenerate and differentiate for growth and repair. TEMRA cells will be co-cultured with mesenchymal stromal cells (progenitor cells from bone) and endothelial progenitor cells (to model vasculature), which would have implications for muscle and bone atrophy seen in spaceflight and the aging population.

Muscle atrophy and Stimulation

Microgravity induces accelerated aging and atrophy of skeletal muscle. Understanding these processes and developing countermeasures would have benefits to the aging population as well as those with neuromuscular disease. Researchers from a startup company, Micro-gRX, are using skeletal muscle tissue chips to study muscle responses to microgravity and whether electrical activity and stimulation can prevent aberrant myocyte changes. These chips contain primary human myocytes from young, and older, healthy and sedentary volunteers grown on top of electrodes which can deliver electrical stimulation. Future studies can test additional therapeutic candidates aimed at deterring muscle atrophy.

Thus, there is tremendous interest in leveraging the microgravity platform in combination with the microphysiological system to model human diseases and drive progress towards better, more effective therapies. You, too, can add space to your portfolio of tools and use Axiom as your guide to develop a novel research strategy for drug discovery efforts.