The lack of gravitational loading is a pivotal risk factor during space flights. Biomedical studies indicate that because of the prolonged effect of microgravity, humans experience bone mass loss, muscle atrophy, cardiovascular insufficiency, and sensory motor coordination disorders. These findings demonstrate the essential role of gravity in human health quality. The physiological and pathophysiological mechanisms of an acute response to microgravity at various levels (molecular, cellular, tissue, and physiological) and subsequent adaptation are intensively studied. Under the permanent gravity of the Earth, multicellular organisms have developed a multi-component tissue mechanosensitive system which includes cellular (nucleo- and cytoskeleton) and extracellular (extracellular matrix, ECM) “mechanosensory” elements. These compartments are coordinated due to specialized integrin-based protein complexes, forming a distinctive mechanosensitive unit. Under the lack of continuous gravitational loading, this unit becomes a substrate for adaptation processes, acting as a gravisensitive unit. Since the space flight conditions limit large-scale research in space, simulation models on Earth are of particular importance for elucidating the mechanisms that provide a response to microgravity. This review describes current state of art concerning mammalian ECM as a gravisensitive unit component under real and simulated microgravity and discusses the directions of further research in this field.

Cell technologies have provided promising tools for modulating the properties of multipotent mesenchymal stem/stromal cells (MSCs) to meet the needs of cell therapy as well as tissue engineering and regenerative medicine (TERM). Ex vivo preconditioning is directed at enhancing the engraftment of MSCs and activating their secretory activity, primarily the production of soluble mediators. The present review aims to highlight the underestimated effect of the most accepted preconditioning approaches on the modification of the important set of insoluble molecules secreted by MSCs into extracellular space—the extracellular matrix (ECM). A thorough review of the published literature was performed, with particular emphasis on ECM-related data. The analysis of data on ECM changes showed that most of the applied preconditioning methods—hypoxia, inflammatory priming, pharmacological agents, 3D culture, and scaffolds—generally stimulate ECM production, increase the deposition of growth factors, promote alignment, and increase ECM stiffness. There are already preliminary results demonstrating the successful application of preconditioned ECM for promoting angiogenesis, targeted stromal lineage differentiation, and other therapeutic goals. The prospects for further research in this area are discussed.

Multipotent mesenchymal stromal cells (MSCs) are used for supplementary therapy of ischemic and inflammatory diseases. After systemic administration, transmigration of MSCs to target tissues is accompanied by their interaction with activated endothelial cells (ECs) at the site of injury. In this study, we investigated the effects of TNF-α-activated ECs on MSC functions under different levels of hypoxia. For this purpose, the short-term direct co-culture of MSCs and activated TNF-α endothelial cells was used. MSCs retained their stromal phenotype and multilineage differentiation potential after the interaction with activated ECs. At the same time, there were detected changes in the expression of molecules involved in MSC contacts with other cells and the extracellular matrix (ECM), as well as in regulating ECM degradation and cell migration. Furthermore, conditioned medium from activated endothelium stimulated targeted and untargeted migration of MSCs. The interaction of MSCs with activated ECs enhanced the paracrine activity of both cell types due to upregulated transcription and elevated levels of pleiotropic cytokines IL-6 and IL-8, and altered the protease–antiprotease balance. These data suggest that short-term interaction of MSCs with activated ECs may play an important role in tissue reparative and remodeling processes. Specifically, it may promote the migratory phenotype of MSCs. In contrast to physiological hypoxia (5% O₂), acute hypoxic stress (0.1% O₂, 24 h) attenuated the stimulatory effects of ECs on MSCs.