Simulated Microgravity: Critical Review on the Use of Random Positioning Machines for Mammalian Cell Culture

Abstract

Random Positioning Machines (RPMs) have been used since many years as a ground-based model to simulate microgravity. In this review we discuss several aspects of the RPM. Recent technological development has expanded the operative range of the RPM substantially. New possibilities of live cell imaging and partial gravity simulations, for example, are of particular interest. For obtaining valuable and reliable results from RPM experiments, the appropriate use of the RPM is of utmost importance. The simulation of microgravity requires that the RPM's rotation is faster than the biological process under study, but not so fast that undesired side effects appear. It remains a legitimate question, however, whether the RPM can accurately and reliably simulate microgravity conditions comparable to real microgravity in space. We attempt to answer this question by mathematically analyzing the forces working on the samples while they are mounted on the operating RPM and by comparing data obtained under real microgravity in space and simulated microgravity on the RPM. In conclusion and after taking the mentioned constraints into consideration, we are convinced that simulated microgravity experiments on the RPM are a valid alternative for conducting examinations on the influence of the force of gravity in a fast and straightforward approach.

Key Proteins Involved in Spheroid Formation and Angiogenesis in Endothelial Cells After Long-Term Exposure to Simulated Microgravity

“…A part of the incubated cells detaches from the bottom of a culture flask and forms 3D aggregates like they are observed after spaceflights [2, 4, 5, 19]. Even though in contrast to a stay in space, sheer forces are produced on the RPM, multicellular spheroids and tubular structures are formed in both conditions [18-20]. …”

TRPC6 in simulated microgravity of intervertebral disc cells

“…Samples are placed at the centre of the frames, where the generated motion pattern is designed to equally distribute the gravity vector spatially and temporally (the gravity mathematically averages zero) [33]. Because the constant reorientation of the gravity vector prevents biological systems to adjust to this force, their response is similar to the one achieved upon real microgravity exposure [16].…”

“…In vitro experiments [13] and animal studies conducted during space flight [14,15] have shown degenerative biomechanical or biochemical effects of microgravity. To study microgravity on Earth, random positioning machines (RPMs) are commonly used [16]. Signs of IVD degeneration were observed in mice discs cultured in a rotary wall vessel bioreactor [17], although this was not the case with rat IVDs [18].…”

Spheroid formation and modulation of tenocyte-specific gene expression under simulated microgravity

“…The exact function of the RPM used in this study has been described in detail elsewhere 13 . Briefly, an incubator had been installed on rotating frames.…”