SCD \u2013 Stem Cell Differentiation Toward Osteoblast Onboard the International Space Station

Abstract

Microgravity produces a variety of physical, chemical, and biological cues leading to an intricate and largely unresolved network of mechanosensitive molecules, transduction pathways, oxidative stress-related responses, and adaptations. The bone loss observed in astronauts and animal models after spaceflight is attributable to alterations in the bone tissue formation that depends on the continuous remodelling through the activities of bone-resorbing osteoclasts of hematopoietic lineage and bone-forming osteoblast of mesenchymal origin. Focusing on osteogenic differentiation, we present the results of the ”SCD - Stem Cells Differentiation” experiment, aiming to determine how human bone marrow stem cells (hBMSCs) react to a prolonged (approx. 2 weeks) exposure to microgravity in terms of growth, and differentiation when treated with a physiological osteo-inducer as 1,25-dihydroxy vitamin D (Vit D3). The experiment was selected by the European Space Agency and transferred to ISS with the Soyuz-TMA- 16M (ISS 42S). It was carefully prepared because experiments performed on ISS remain a uniquely exceptional means of clarifying the microgravitational effects on osteogenesis, often only partially activated and detectable under simulated conditions. Because of the substantial reduction in calcification observed (about 50% inflight vs. on-ground control), we looked at significantly affected pathways in hBMSCs grown in microgravity vs. on-ground controls. Genome-wide expression changes were assessed via microarray and next generation sequencing (NGS) and integrated with exosomal mi-RNA measurements. Multi-scale pathway analysis of the omics datasets revealed evidence of cell cycle arrest, occurring with a number of osteogenic gene markers, but without indications of adipogenesis, senescence and/or apoptosis.