Application of Microgravity Environment to Mesenchymal Stem Cells Culture and Cartilage Regeneration

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A three-dimensional (3D) clinostat is a device for multi-direction G force generation, which produces an environment with an average of 10-3 G over time. Behavior of human somatic cells under microgravity environment is only poorly understood and is unexpectable showing ignorance of our knowledge. We report here that human mesenchymal stem cells (hMSCs) in the 3D-clinostat (group CL) proliferated more extensively than those in normal 1G environment (group C). FACS showed that the number of hMSCs double-positive for CD 44/CD 29 or CD 90/CD 29 were 6-times higher in group CL as compared with group C after 7 days culture. Telomere length of hMSCs did not change during culture periods in both groups, CL and C. Telomerase activity was undetectable level in all these hMSC cells. The expression levels of type II collagen, aggrecan increased in the group C but decreased and could not be detected in the group CL. Phosphorylation of ERK1/2 was increased and p38MAPK was repressed in the group CL being consistent with stimulated proliferation and inhibited differentiation. When the pellets of hMSCs were explanted into the cartilage defect made in the intercondylar fossa of the mouse femur, the transplants from group CL formed hyaline cartilage after 7 days, whereas the transplants from group C formed non-cartilage tissue containing a small number of cells. These results show that hMSCs cultured in a 3D-clinostat extensively proliferate with characteristics of stem cells keeping their ability to differentiate into hyaline cartilage after transplantation, which cannot be performed by culturing in 1G condition. Simulated microgravity may be useful for the expansion of stem cells in vitro and could be applicable for regeneration medicine and developmental biology.