Behavior of Stem-Like Cells, Precursors for Tissue Regeneration in Urodela, Under Conditions of Microgravity

Abstract

We summarize data from our experiments on stem-like cell-dependent regeneration in amphibians in microgravity. Considering its deleterious effect on many tissues, we asked whether microgravity is compatible with reparative processes, specifically activation and proliferation of source cells. Experiments were conducted using tailed amphibians, which combine profound regenerative capabilities with high robustness, allowing an in vivo study of lens, retina, limb, and tail regeneration in challenging settings of spaceflight. Microgravity promoted stem-like cell proliferation to a varying extent (up to 2-fold), and it seemed to speed up source cell dedifferentiation, as well as sequential differentiation in retina, lens, and limb, leading to formation of bigger and more developed regenerates than in 1g controls. It also promoted proliferation and hypertrophy of Müller glial cells, eliciting a response similar to reactive gliosis. A significant increase in stem-like cell proliferation was mostly beneficial for regeneration and only in rare cases caused moderate tissue growth abnormalities. It is important that microgravity yielded a lasting effect even if applied before operations. We hypothesize on the potential mechanisms of gravity-dependent changes in stem-like cell behavior, including fibroblast growth factor 2 signaling pathway and heat shock proteins, which were affected in our experimental settings. Taken together, our data indicate that microgravity does not disturb the natural regenerative potential of newt stem-like cells, and, depending on the system, even stimulates their dedifferentiation, proliferation, and differentiation. We discuss these data along with publications on mammalian stem cell behavior in vitro and invertebrate regeneration in vivo in microgravity. In vivo data are very scarce and require further research using contemporary methods of cell behavior analysis to elucidate mechanisms of stem cell response to altered gravity. They are relevant for both practical applications, such as managing human reparative responses in spaceflight, and fundamental understanding of stem cell biology.

Repeated ecological and life cycle transitions make salamanders an ideal model for evolution and development

“…Genomic expansion also results in a reduced rate of cellular differentiation. This is hypothesized to maintain “younger” stem cell populations, which should have a high capacity for tissue regeneration 176,177 . However, slower regeneration rates are observed in obligately paedomorphic lineages with the highest degrees of extreme genome expansions, suggesting that large genomes aid the regeneration process, but it may take a long time 177 .…”

Effects of Spaceflight and Simulated Microgravity on YAP1 Expression in Cardiovascular Progenitors: Implications for Cell-Based Repair

“…Simulated microgravity studies are currently being performed by several laboratories, and in some cases, the opportunity to directly compare simulated microgravity findings with similar studies performed on the ISS has provided insight regarding where similarities and differences may be expected [9,10]. Simulated microgravity is achieved through the use of clinostats, which are devices that rotate cells continuously around one axis, 2D, perpendicular to the force of gravity, or two axes, 3D, to achieve weightlessness similar to the weightlessness experienced in space [11,12].…”

Pigment Epithelia of the Eye: Cell-Type Conversion in Regeneration and Disease

“…During the active proliferation of IPE cells in situ, in parallel with dedifferentiation, there is neither uncontrolled growth nor disturbance of the lens’ regeneration and morphogenesis, even in the case of repeated lens removals [ 63 ]. The rare cases of tumor formation are shown to be associated with exposure to carcinogens [ 64 ] and also occur in newts exposed to low gravity conditions [ 65 ].…”