Transduced Stromal Co-Cultures of Human Bone Marrow in Microgravity (Space Tango-Hematopoietic Stem Cells) investigates aging in blood stem cells and the transformation of these cells into cancer cells. While stem cells play a vital role during embryonic and fetal development, they also maintain adult tissue integrity and can be mobilized in response to injury to repair and regenerate tissues. Stem Cells are defined functionally based on their capacity to self-renew (divide without differentiating), differentiate into tissue-specific progenitors, and become dormant in protective microenvironments. This experiment design allows the ability to simulate and observe the response to injury and capacity for repair, aging, and (pre-)malignant transformation of normal hematopoietic stem cells in an accelerated time frame.
Results may provide valuable insights into the maintenance of hematopoietic stem cell health and functionality, response to injury through the accumulation of mutations, and, lastly, the mechanisms fueling long-term (pre-)malignant transformation into leukemia stem cells.
Exposure to radiation and microgravity in low-Earth orbit can speed up both processes, simulating aging and enabling the study of cell response to injury, capacity for repair, overall stem cell fitness, and evolution of blood cancers. Changes are expected to be seen in the mutational profile in the normal hematopoietic stem cells sent to space aboard the International Space Station (ISS) to use the microgravity environment to simulate and study accelerated aging.
Human Muscle Contraction Response in Microgravity (Human Muscle-on-Chip) tests the feasibility of using accelerated muscle weakness in space to study age-related muscle decline on Earth, a condition also known as sarcopenia. This investigation uses tissue chips, small devices that contain human cells in a three-dimensional matrix designed to model both the structure and function of human tissue and organs.
Age-related muscle loss, a condition referred to as sarcopenia, is a significant concern to human health on Earth. This condition can reduce one’s ability to perform physical activities such as walking and running. While sarcopenia is present with increased prevalence among the aging population, it remains poorly understood. The Human Muscle-on-Chip investigation has the potential to improve our understanding of sarcopenia and identify therapeutics that may reduce the effects of muscle loss for humans on Earth and in Space.
The research is funded by the National Institute of Health National Center for Advancing Translational Sciences (NIH/NCATS) as is a part of their Tissue Chips in Space program. This is the second flight in a series of investigations for Dr. Siobhan Malany and the University of Florida.
Muscle loss is accelerated in microgravity, providing a unique opportunity to study muscle degeneration and evaluate potential therapeutics to counteract sarcopenia in an increasingly aged population on Earth.
Study of Induced Pluripotent Stem Cells (iPSCs) in Microgravity (Production of Stem Cells for Personalized Medicine) examines the effect of microgravity on induced pluripotent stem cells (iPSCs) cells and the neural progenitor cells they generate. iPSCs may be created from any person of any age simply by taking a skin or blood sample, isolating cells, giving the cells specific factors, and driving them back to an embryonic state. iPSCs are immortal (can be grown forever) and have the capacity to create any tissue of the human body. iPSCs are ideal for creating and testing potential treatments that can be exactly tailored to the individual.
Growing iPSC cells for use in treating humans is a complex process. On Earth, there are problems with efficient growth and division of the stem cells (proliferation) and then turning them into specific cell types of the human body such as beating heart cells and neurons in the brain (differentiation). Enhancing this process is beneficial to the human population if it results in improved stem cells.
If stem cells can be grown more effectively in microgravity and if the process can be scaled up for the biomanufacturing of key cellular products that can treat humans, this new capability will be important for people on Earth.
The Effects of Microgravity on Microglia 3-Dimensional Models of Parkinson’s Disease and Multiple Sclerosis – Mission 2 (Cosmic Brain Organoids) examines the growth and movement of microglial cells in 3D organoids and potential changes in gene expression and protein secretion caused by microgravity.
Parkinson’s disease and multiple sclerosis (MS) are not developmental disorders, and modeling these disease states in vitro is difficult even with advances in reprogramming technologies. More complex organoid models containing multiple cell types and fully mature cells are used to better represent disease progression, allowing for a more suitable platform for the development of potential therapies.
The Research Team conducted the first long-term cultures of patient-specific neural cells in low Earth-orbit by combining induced pluripotent stem cell (iPSC)-derived microglia and dopaminergic, or cortical neurons, into 3D organoids. The first proof-of-principle investigation involved four iPSC lines derived from one person with Parkinson’s disease (dopaminergic organoids), one person with progressive MS (cortical organoids), and two age/sex-matched healthy controls. Significant differences were observed in gene expression and protein secretion associated with exposure to microgravity in both dopaminergic and cortical organoids. These results, and this follow-on mission to the groundbreaking study, are laying the foundation for further and more complex studies to dissect the fundamental mechanisms underlying neuroinflammation and neurodegenerative diseases and understand the impact of microgravity on these disease-relevant processes.
Exposure to microgravity and radiation, as occurs on the International Space Station, causes significant mechanical unloading of mammalian tissues, resulting in rapid physiological alterations.
The Effect of Microgravity on Human Brain Organoids (Space Tango-Human Brain Organoids) will study human brain organoids in space where the physical force of gravity is not present, allowing for a more detailed study of the survival, health, and genetics not possible on Earth. Organoids are small, three-dimensional stem cell-derived living masses of cells. Scientists use human organoids to model a specific organ’s biological functions as its cells interact with their environment and mature. Brain organoids may be used for a variety of studies including understanding the effects of diseases, aging, and drug interactions in the brain. The results of Space Tango-Human Brain Organoids are expected to advance organoid technology, enabling a wide variety of new experiments using organoids in microgravity as a test platform for stress on the brain.
This investigation is also known as BOARDS2 – Brain Organoids Advanced Research and Development in Space – and is the third flight in a series of investigations for UCSD.
The results of this study demonstrate how exposure to microgravity changes the survival, metabolism, and neuronal features of brain cells. In addition, understanding how the brain responds and adapts to the stresses of space including the absence of gravity is essential for any crewed space mission. This is fundamental to protecting human health for space exploration as it paves the way for future research on how the brain responds to spaceflight.