Hypergravity Stimulation Enhances PC12 Neuron-Like Cell Differentiation

Abstract

Altered gravity is a strong physical cue able to elicit different cellular responses, representing a largely uninvestigated opportunity for tissue engineering/regenerative medicine applications. Our recent studies have shown that both proliferation and differentiation of C2C12 skeletal muscle cells can be enhanced by hypergravity treatment; given these results, PC12 neuron-like cells were chosen to test the hypothesis that hypergravity stimulation might also affect the behavior of neuronal cells, in particular promoting an enhanced differentiated phenotype. PC12 cells were thus cultured under differentiating conditions for either 12 h or 72 h before being stimulated with different values of hypergravity (50 g and 150 g). Effects of hypergravity were evaluated at transcriptional level 1 h and 48 h after the stimulation, and at protein level 48 h from hypergravity exposure, to assess its influence on neurite development over increasing differentiation times. PC12 differentiation resulted strongly affected by the hypergravity treatments; in particular, neurite length was significantly enhanced after exposure to high acceleration values. The achieved results suggest that hypergravity might induce a faster and higher neuronal differentiation and encourage further investigations on the potential of hypergravity in the preparation of cellular constructs for regenerative medicine and tissue engineering purposes.

Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight

“…For decades, it has been known that hypergravity promotes cell proliferation (47,48). In recent years, effects on differentiation and proliferation similar to those of hypergravity have been reported in human endothelial cells (49), myoblasts (50), and neuron-like cells (51). Vibration has also been reported to affect cell proliferation (52) and may have also contributed to the fast growth of the cells fixed on d 3.…”

Mechanical load increase–induced changes in cytoskeletal structure and cellular barrier function in human cerebral endothelial cells

“…Increased gravitational force is commonly regarded to be harmful and noxious. However, several previous studies have shown that hypergravity has various beneficial effects on living organisms, such as enhancing the immune functions in mouse with allergic diseases, differentiation of the bone marrow mesenchymal stem cells into cardiac muscle and neuronal cells, and increasing the osteopontin expression in osteoblasts (Genchi et al, ; Jang, Jung, & Kim, ; Ling et al, ; Zhou, Zu, Sun, Zhuang, & Yang, ).…”

Hypergravity As a Tool for Cell Stimulation: Implications in Biomedicine

“…Scale bar is 50 µm. (C) Reproduced and adapted with permission from Hindawi (Genchi et al, 2015). Effect of hypergravity (2.9 g, 4 weeks) on bone structure of ovariectomized rats.…”