# Changes in the Cell Division of Chang Liver Cells Induced by Simulated Microgravity
## 4 Discussion  
Previous studies have demonstrated changes in mammalian cells under SMG conditions. [PERSON] and colleagues studied the biological effects (including the proliferation of cells, cell cycle progression, the differentiation and adhesion of cells, apoptosis, and the integrity of the genome) of SMG on mouse embryonic cells. The results showed that mouse embryonic cells are very sensitive to microgravity and can rapidly adjust to adapt to the conditions of microgravity [25]. [PERSON] and colleagues used a random positioning machine (RPM) to study the effect of simulated microgravity on Jurkat cells. The results showed that the viability of Jurkat cells decreased after microgravity simulation [26]. The liver is a very important organ of essential metabolic processes; it interacts with almost every tissue in the human body. Previous studies have shown that the liver of rodents is very sensitive and susceptible to physical conditions during spaceflight or experiments on the ground using a microgravity simulator [27]. Long-term spaceflight should be thoroughly studied for liver metabolic processes and the gut-liver axis to help enhance and maintain metabolic equilibrium [27]. Long-term cultures of human liver cells can be established in simulated microgravity conditions, which will also make it possible to study how the liver regenerates and how cells interact in a way that is similar to processes in the body [28]. [PERSON] and colleagues demonstrated that SMG treatment also induces changes in Loureirin B metabolism and the expression of primary cytochrome P450 in the rat liver [29]. [PERSON] and colleagues showed that microgravity causes the dysregulation of lipids in the liver of mice [30]. SMG could be useful for creating hepatic devices developed from human hepatic cells and progenitor cells. SMG promotes the development of 3D cultures of human hepatic cells and progenitor cells, as well as the preservation of stemness over cell differentiation; these effects were linked to the stimulation of glycolytic metabolism [31]. Figure 6: Microtubule staining of CCL-13 cells: (**a–f**). The appearance of the spindle in the control CCL-13 cells (**g–l**). The appearance of the spindle in the CCL-13 cells in the SMG group. Together with cellular development and division, cells move through the cell cycle. A cell spends the majority of its time in the interphase, a phase where it develops and gets ready to divide. The cell completes both mitosis and division after overcoming the interphase [32]. In the initiation of mitosis, cells get ready to divide in the G1 phase. After that, they move into the S phase, and during which the cell replicates its whole DNA. The cell moves into the G2 phase, where it begins to arrange and condense the genetic material in preparation for division. The M phase follows. At this time, sister chromatids are separated from each other, and one copy of the chromosome is given to each daughter cell. [33]. The present study found that the CCL-13 cells in the SMG group showed an increase in the cell percentage in the G0/G1 phase and reduced cells in the S phase and G2/M phase. SMG exposure induces a delay of CCL-13 cells in the G0/G1 phase and slows down the process of cells entering the division phase, which drives these cells into the arrest phase of the cell cycle, and reduces the division of the cells. During mitosis, cells exhibit morphological changes in the cytoplasm and nucleus [34; 35]. A previous study reported that a high nuclear/ cytoplasmic ratio starts the intracellular processes that get the cell ready for division, and cytoplasmic expansion continues until the moment of division [36]. In this investigation, SMG-induced CCL-13 cells showed cell area expansion and nuclear area reduction, leading to a reduction in the nuclear/cytoplasmic ratio. This revealed that a low nuclear/cytoplasmic ratio is correlated with a delay in entering the division phase for CCL-13 cells under SMG conditions.