Mechanical strain modulates age-related changes in the proliferation and differentiation of mouse adipose-derived stromal cells.
BACKGROUND
Previous studies on the effects of aging in human and mouse mesenchymal stem cells suggest that a decline in the number and differentiation potential of stem cells may contribute to aging and aging-related diseases. In this report, we used stromal cells isolated from adipose tissue (ADSCs) of young (8-10 weeks), adult (5 months), and old (21 months) mice to test the hypothesis that mechanical loading modifies aging-related changes in the self-renewal and osteogenic and adipogenic differentiation potential of these cells.


RESULTS
We show that aging significantly reduced the proliferation and increased the adipogenesis of ADSCs, while the osteogenic potential is not significantly reduced by aging. Mechanical loading (10% cyclic stretching, 0.5 Hz, 48 h) increased the subsequent proliferation of ADSCs from mice of all ages. Although the number of osteogenic colonies with calcium deposition was increased in ADSCs subjected to pre-strain, it resulted from an increase in colony number rather than from an increase in osteogenic potential after strain. Pre-strain significantly reduced the number of oil droplets and the expression of adipogenic marker genes in adult and old ADSCs. Simultaneously subjecting ADSCs to mechanical loading and adipogenic induction resulted in a stronger inhibition of adipogenesis than that caused by pre-strain. The reduction of adipogenesis by mechanical strain was loading-magnitude dependent: loading with 2% strain only resulted in a partial inhibition, and loading with 0.5% strain could not inhibit adipogenesis in ADSCs.


CONCLUSIONS
We demonstrate that mechanical stretching counteracts the loss of self-renewal in aging ADSCs by enhancing their proliferation and, at the same time, reduces the heightened adipogenesis of old cells. These findings are important for the further study of stem cell control and treatment for a variety of aging related diseases.
Huang
See-Chang
SC
Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
Wu
Tzu-Chin
TC
Yu
Hsiao-Chi
HC
Chen
Mei-Ru
MR
Liu
Chun-Min
CM
Chiang
Wen-Sheng
WS
Lin
Kurt M
KM
D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D016922:Cellular Senescence; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D013314:Stress, Mechanical; D017154:Stromal Cells / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D006023:Glycoproteins; D047495:PPAR gamma; C493716:Runx2 protein, mouse; C029490:nephrocalcin