Biomedical advances in three dimensions: An overview of human cellular studies in space and spaceflight analogues

Abstract

Many of the underlying causes of human disease result from the effects of physical/mechanical forces acting on living cells. However, the constant overriding force of gravity precludes our ability to identify the full spectrum of cellular responses to mechanical forces that dictate the transition between homeostasis and disease. Cell and tissue culture studies in true spaceflight or in the Rotating Wall Vessel (RWV) spaceflight analogue bioreactor offer dynamic approaches to engineer high fidelity, physiologically relevant 3-D tissue models with a vast array of biomedical applications. These organotypic models have furthered our understanding of structure-function relationships and design principles of the cellular microenvironment and cellular biomechanics that are critical in establishment of in vitro models that better recapitulate in vivo responses as compared to conventional flat 2-D cultures, and have complemented and advanced the knowledge being gained from other 3-D cell culture approaches. The applications of tissue engineering research in true spaceflight and the RWV are as diverse as the number of cell types that can be cultured using these platforms, and hold the potential to help us better understand organogenesis and normal tissue development using cell lines, stem cells, and primary cells, as well as disease pathologies, including infectious disease, immunological disorders, and cancer. Accordingly, these studies have shown tremendous potential to accelerate our understanding of human physiology and susceptibility to disease and hold translational promise to benefit mankind on Earth. In addition, studying the response of mammalian cells to culture under microgravity and microgravity analogue conditions provides the opportunity to unveil underpinning mechanisms regulating spaceflight-induced alterations in human physiology, adaptation during long duration missions, and associated clinical problems for astronauts.