Abstract
Human cells, when exposed to both real and simulated microgravity (s-µg), form 3D tissue constructs mirroring in vivo architectures (e.g., cartilage, intima constructs, cancer spheroids and others). In this study, we exposed human foetal osteoblast (hFOB 1.19) cells to a Random Positioning Machine (RPM) for 7 days and 14 days, with the purpose of investigating the effects of s-µg on biological processes and to engineer 3D bone constructs. RPM exposure of the hFOB 1.19 cells induces alterations in the cytoskeleton, cell adhesion, extra cellular matrix (ECM) and the 3D multicellular spheroid (MCS) formation. In addition, after 7 days, it influences the morphological appearance of these cells, as it forces adherent cells to detach from the surface and assemble into 3D structures. The RPM-exposed hFOB 1.19 cells exhibited a differential gene expression of the following genes: transforming growth factor beta 1 (TGFB1, bone morphogenic protein 2 (BMP2), SRY-Box 9 (SOX9), actin beta (ACTB), beta tubulin (TUBB), vimentin (VIM), laminin subunit alpha 1 (LAMA1), collagen type 1 alpha 1 (COL1A1), phosphoprotein 1 (SPP1) and fibronectin 1 (FN1). RPM exposure also induced a significantly altered release of the cytokines and bone biomarkers sclerostin (SOST), osteocalcin (OC), osteoprotegerin (OPG), osteopontin (OPN), interleukin 1 beta (IL-1β) and tumour necrosis factor 1 alpha (TNF-1α). After the two-week RPM exposure, the spheroids presented a bone-specific morphology. In conclusion, culturing cells in s-µg under gravitational unloading represents a novel technology for tissue-engineering of bone constructs and it can be used for investigating the mechanisms behind spaceflight-related bone loss as well as bone diseases such as osteonecrosis or bone injuries.
Highlights
Real microgravity in space can affect the health of astronauts after an extended period of time on the international space station (ISS) or other future platforms allowing a sojourn in orbit [1]
Within the same culture flask, one group of the cells developed in the form of an adherent monolayer and the other group formed several 3D bone constructs or multicellular spheroids (MCS)
We investigated the release of tumour necrosis factor alpha (TNF-α), which is a cytokine involved in the regulation of a wide spectrum of biological processes, including cell proliferation, differentiation, apoptosis, lipid metabolism and coagulation [84]
Summary
Real microgravity in space can affect the health of astronauts after an extended period of time on the international space station (ISS) or other future platforms allowing a sojourn in orbit [1]. Studies of terrestrial organisms exposed to real (r-μg) or simulated microgravity (s-μg) face multiple challenges, as even experiments with cells under r-μg conditions are rather rare and expensive For this reason, researchers have developed simulation devices, such as the 2D clinostat (CN), the NASA-developed rotating wall vessel (RWV) bioreactor, the random positioning machine (RPM) and the magnetic levitator, among others, to prepare for spaceflights and to conduct ground-based space research on stem cells and specialized cells [1,2,3]. RPMs are like clinostats or rotating wall vessel bioreactors, ground-based facilities constructed to simulate microgravity on the Earth’s surface (1 g) Their working principle is based on a gravity vector averaging to zero over time [4]. The RPM is used worldwide for tissue-engineering purposes for various cell types and is an accepted model in preparing for future spaceflight missions [1,8]
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