Factors implicating the validity and interpretation of mechanobiology studies in simulated microgravity environments

Abstract

Simulated microgravity (s-μg) devices provide unique conditions for elucidating the effects of gravitational unloading on biological processes and are increasingly being applied for mechanobiology studies. However, without proper characterization of the mechanical environment generated by these systems, the interpretation of results is confounded and limited. Furthermore, the cell culture approaches central to s-μg experimentation introduces new factors that can fundamentally affect results, but these are currently not addressed. It is essential to understand the complete culture environment and how constituent conditions can individually and synergistically affect cellular responses in order to correctly interpret results, otherwise outcomes may be misattributed to the effects of microgravity alone. For the benefit of the growing space biology community, this article critically reviews a typical s-μg cell culture environment in terms of three key conditions: fluid-mediated mechanical stimuli, oxygen tension and biochemical. These and the implications of other experimental variables for biological analysis are categorically discussed. A new set of controls is proposed to properly evaluate the respective effects of these conditions in s-μg culture, along with a reporting matrix and potential strategies for addressing the current limitations of simulated microgravity devices as a platform for mechanobiology research.

Cytoskeletal Remodeling Mimics Endothelial Response to Microgravity

“…Our studies might have implications also in other contexts. Indeed simulating microgravity is becoming a useful tool to unveil the role of mechanical stimuli in health and disease ( Poon, 2020 ) and to optimize protocols for tissue engineering and regenerative medicine ( Grimm et al, 2018 ), thus answering the questions raised by Rinaldi (2016) about the meaning of space research.…”

Impairment of 7F2 osteoblast function by simulated partial gravity in a Random Positioning Machine

“…To simulate reduced gravity, all experiments were carried out in the second generation of the software-driven Random Positioning Machine (RPM SW 2.0) (originally DutchSpace Airbus, Leiden, Netherlands, now Yuri GmbH, Meckenbeuren, Germany). The Mode of operation of this RPM differs from that of the earlier generation, which was developed for generating completely random paths, thus creating a simulated microgravity condition, and used for years in research 18 – 20 . The “mode of operation” of the RPM SW for simulating micro and partial gravity (see Supplementary Fig.…”

“…While alternatives like parabolic flights exist for short-term studies, the experimental gold standards for simulating microgravity on Earth are rotating clinostats 16 or microgravity-simulating bioreactors 12 , 17 . There is ample evidence in the literature suggesting that the results of ground-based modeled microgravity studies mimic real space conditions 18 – 20 . In comparative studies, similar degrees of inhibition of proliferation and differentiation have been observed both in osteoblast-like cells cultured in true-microgravity in space as well as in experiments carried out in simulated microgravity using clinostats 21 .…”

Cancer Studies under Space Conditions: Finding Answers Abroad

“…The different means to simulate µ g on Earth is a source of heterogeneity in the studies analysing the effects of µ g on cancer cells. For a recent discussion of the different forces a cell is exposed in these devices, see the recent review by Poon [ 33 ].…”