SHAPE: Investigating innate immunity in real microgravity aboard the International Space Station using advanced human bone marrow organoids.

Abstract

In 2025, NASA through their Artemis program aims to send humans beyond Low-Earth Orbit for the first time since 1972. As focus on space exploration shifts from the International Space Station (ISS) to targets farther away, the impact of long-duration space travel on the human body and the ability to withstand these effects are becoming the primary factors precluding further expansion of humanity’s reach into space. The space environment poses numerous unique challenges to astronauts, with typical examples including immune dysfunction and the loss of bone density. Advanced bone marrow organoids comprised of primary human mesenchymal and hematopoietic stem cells were developed to investigate links between those two phenomena in real microgravity aboard the ISS. The unique spatial requirements necessitated development of a novel system, termed Hydrowells, to facilitate the long-term culture and subsequent fixation of many organoids in a small volume, remotely. Validating Hydrowells as a suitable system for 3D in vitro experiments in space allows for future experiments with diverse model systems.The SHAPE project flew over 2,000 organoids to the ISS to investigate innate immunity in vitro in real microgravity. Morphological analysis demonstrated compact organoids with a hematopoietic stem cell niche under earth gravity while space led to looser cell aggregates. The ISS data will be compared to samples cultured in simulated microgravity, centrifuge controls, and earth gravity. Furthermore, MACE-sequencing (Massive Analysis of cDNA Ends) is currently underway to provide insight into the effects of different gravitational conditions on gene expression regarding innate immunity.Technical insight from SHAPE and the Hydrowells facilitates future 3D in vitro experiments in real microgravity with culture systems as diverse as gastruloids. The results from SHAPE will increase understanding of the interplay between innate immunity and bone morphology in space, enabling the mitigation of health risks to astronauts and freeing humanity to explore our galaxy further.