Stem cell health and tissue regeneration in microgravity

Abstract

Exposure to microgravity causes significant mechanical unloading of mammalian tissues, resulting in rapid alterations of their physiology, which poses a significant risk for long-duration manned spaceflight. The immediate degenerative effects of spaceflight we understand best are those studied during short-term low-Earth-orbit experiments, and include rapid microgravity-adaptive bone and muscle loss, loss of cardiovascular capacity, defects in wound and bone fracture healing, and impaired immune function. Over the long-term, exposure to microgravity may cause severe deficits in mammalian stem cell-based tissue regenerative health, including, osteogenesis, hematopoiesis, and lymphopoeisis, as well as cause significant stem cell-based tissue degeneration in amphibian tail and lens regeneration. To address the needs for stem cell and other cell science research on the International Space Station (ISS), NASA has developed the new Bioculture System that will allow investigators to initiate and conduct on-orbit experiments that astronauts will be able to monitor and interact with during the course of cell cultures. This cell culture capability combined with advanced technologies for molecular biology and on-orbit measurement of gene expression (WetLab2) and other tools that are now coming online bring the ISS National Laboratory a step closer to becoming a fully functional space laboratory for advancing space biological sciences.

FIG. 1.

The experimental models used to study stem cells in space include the regenerating tail in the newt (Pleurodeles waltl) (A), which contains rapidly proliferating blastema-derived tissue-specific de-differentiated stem cells shown here labeled in red with BrdU (B); mouse embryonic stem cells (C), differentiated into embryoid bodies during spaceflight (D); and mouse bone marrow (E), where hematopoietic (F) and mesenchymal stem cell lineage differentiation have been investigated using cell and molecular approaches.

FIG. 2.

The NASA Bioculture System consists of a docking station housing and supporting 10 independent cell culture cassettes, (A) designed for the ISS express rack. Each durable cassette contains an internal disposable flow path (B) consisting of media bags, a hollow fiber bioreactor, and fluidic components, including tubing, pumps, and valves. The bioreactor (C) is uniquely capable of delivering nutrients and removing waste through diffusion without direct mechanostimulatory fluid flow in contact with the cells, and supports cell adhesion to fibers or to matrix-coated alginate microcarrier beads such as in nonproliferating human induced pluripotent stem cells-derived cardiomyocytes (D), or proliferating osteocytic cultures (E).