Microgravity Potentiates Stem Cell Proliferation While Sustaining the Capability of Differentiation

Abstract

A three-dimensional (3D) clinostat is a device for generating multidirectional G force, resulting in an environment with an average of 10(3) G. Here we report that human mesenchymal stem cells (hMSCs) cultured in a 3D-clinostat (group CL) showed marked proliferation (13-fold in a week) compared with cells cultured under normal conditions of 1 G (group C) (4-fold in a week). Flow cytometry revealed a 6-fold increase in the number of hMSCs double-positive for CD44/CD29 or CD90/CD29 in group CL after 7 days in culture, compared with group C. Telomere length remained the same in cells from both groups during culturing. Group C cells showed increasing expression levels of type II collagen and aggrecan over the culture period, whereas group CL cells showed a decrease to undetectable levels. Pellets of hMSCs from each group were explanted into cartilagedefective mice. The transplants from group CL formed hyaline cartilage after 7 days, whereas the transplants from group C formed only noncartilage tissue containing a small number of cells. These results show that hMSCs cultured in a 3D-clinostat possess the strong proliferative characteristic of stem cells and retain their ability to differentiate into hyaline cartilage after transplantation. On the contrary, cells cultured in a 1-G environment do not maintain these features. Simulated microgravity may thus provide an environment to successfully expand stem cell populations in vitro without culture supplements that can adversely affect stem cell-derived transplantations. This method has significant potential for regenerative medicine and developmental biology.

The simulated microgravity enhances multipotential differentiation capacity of bone marrow mesenchymal stem cells

“…Microgravity, as one of the most important elements of space flight, has been reported to cause extensive physiological changes in MSCs, including the maintenance of the undifferentiated state of BMSCs and potentiating the proliferation and differentiation of the cells to a single direction (Yuge et al 2006(Yuge et al , 2011. In this study, we further demonstrated that SMG could enhance the multipotential differentiation capacity of BMSCs which enriches the previous studies.…”

“…This result further demonstrated that there was some interplay between the geometric cues of the cells and their functions (Kilian et al 2010). While previous report illustrated that SMG was helpful to expand stem cell populations in vitro (Yuge et al 2006), our work further demonstrated that SMG enabled cells to maintain pluripotency and therefore enhance multipotential differentiation capacity.…”

“…We also agree with that the change of the multipotential differentiation capacity of stem cell may be relevant to the telomerase activity. But, results reported by Yuge et al (2006) showed that telomere length for the NG group or the SMG group did not change during culturing, and telomerase activity was undetectable in both groups in their study. The specific effect of the telomerase activity on the multipotential differentiation capacity of stem cell is unclear.…”

Microgravity, Stem Cells, and Embryonic Development: Challenges and Opportunities for 3D Tissue Generation

“…Similar conflicting results were generated using multilineages bone marrow mesenchymal stem cells (MSCs). Human MSCs cultured in SMG (clinostat) increased proliferation and differentiate toward a chondrogenic phenotype upon transplantation in cartilagedeficient rats (Yuge et al, 2006). In contrast, rat MSCs in SMG (clinostat) reduce their proliferation and ability to differentiate toward a chondrogenic fate (Yan et al, 2015).…”

Effects of simulated weightlessness on cellular morphology and biological characteristics of cell lines SGC-7901 and HFE-145

“…Regarding the biological characteristics of normal cells, microgravity could block the cell cycle in human osteoblast cells (Blaber et al, 2013) and potentiate stem cell proliferation, while sustaining the capacity for differentiation (Yuge et al, 2006). Cell cycle control proteins in human T lymphocytes showed altered microgravity (Thiel et al, 2012).…”