Impact of Simulated Microgravity on Oligodendrocyte Development: Implications for Central Nervous System Repair

Abstract

We have recently established a culture system to study the impact of simulated microgravity on oligodendrocyte progenitor cells (OPCs) development. We subjected mouse and human OPCs to a short exposure of simulated microgravity produced by a 3D-Clinostat robot. Our results demonstrate that rodent and human OPCs display enhanced and sustained proliferation when exposed to simulated microgravity as assessed by several parameters, including a decrease in the cell cycle time. Additionally, OPC migration was examined in vitro using time-lapse imaging of cultured OPCs. Our results indicated that OPCs migrate to a greater extent after stimulated microgravity than in normal conditions, and this enhanced motility was associated with OPC morphological changes. The lack of normal gravity resulted in a significant increase in the migration speed of mouse and human OPCs and we found that the average leading process in migrating bipolar OPCs was significantly longer in microgravity treated cells than in controls, demonstrating that during OPC migration the lack of gravity promotes leading process extension, an essential step in the process of OPC migration. Finally, we tested the effect of simulated microgravity on OPC differentiation. Our data showed that the expression of mature oligodendrocyte markers was significantly delayed in microgravity treated OPCs. Under conditions where OPCs were allowed to progress in the lineage, simulated microgravity decreased the proportion of cells that expressed mature markers, such as CC1 and MBP, with a concomitant increased number of cells that retained immature oligodendrocyte markers such as Sox2 and NG2. Development of methodologies aimed at enhancing the number of OPCs and their ability to progress on the oligodendrocyte lineage is of great value for treatment of demyelinating disorders. To our knowledge, this is the first report on the gravitational modulation of oligodendrocyte intrinsic plasticity to increase their progenies.

Simulated microgravity enhances oligodendrocyte mitochondrial function and lipid metabolism

“…The only visible difference between conditions was the greater cell number in cultures exposed to sim‐µG as shown (Fig. ), as expected based on our previous study (Espinosa‐Jeffrey et al, ).…”

“…We have started to unravel how biological processes in the CNS occur in weightlessness. We have previously shown that the cell cycle is shortened and that more OLPs are produced in microgravity (Espinosa‐Jeffrey et al, ). Here we sought to determine the metabolic status of OLPs when exposed to sim‐µG for 72 hr.…”

“…Human fetal cortical tissue samples (17 weeks' gestation) were used as the source of neural progenitors. We previously reported the human cell culture preparation (Espinosa‐Jeffrey et al, ) that is described in Figure . We have previously designed a series of developmental stage–specific chemically defined “stem” cell culture media for neural stem cell (NSC) propagation and maintenance of their pluripotent stage (Espinosa‐Jeffrey et al, ).…”

“…We subjected rodent and human OLPs to short exposures (24–72 hr) to sim‐µG and revealed that OLPs displayed an enhanced and sustained proliferation with a concomitant shortening of the cell cycle in sim‐µG by using BrdU and time‐lapse microscopy. Exposure to sim‐µG also increased the migratory properties of the OLPs (Espinosa‐Jeffrey et al, ).…”

Consequences of Simulated Microgravity in Neural Stem Cells: Biological Effects and Metabolic Response

“…We also investigate the effects of the return to normal gravity after SM, giving a proof of principle of the reversible effects of SM on neural stem cells. There are few papers that explore the effects of microgravity on stem cells: most efforts were conducted in the understanding of the effects of SM on hematopoietic stem cells and muscle and bone precursors [2,4,30,31]; in addition, reports have examined changes that occur in mouse embryonic stem cells [7] and oligodendrocyte precursors [32]. Few reports address the effects of microgravity on stem cells or precursors of the neural lineage.…”