TY - JOUR
T1 - Beta-adrenoceptor pathway enhances mitochondrial function in human neural stem cells via rotary cell culture system
AU - Chiang, Ming Chang
AU - Lin, Heng
AU - Cheng, Yi Chuan
AU - Yen, Chia Hui
AU - Huang, Rong Nan
AU - Lin, Kuan Hung
N1 - Funding Information:
We thank Chia-Nan, Yen for proofreading and editing the manuscript. This work was supported by grants from the National Science Council ( NSC97-2320-B-034-001-MY2 and NSC99-2320-B-030-008-MY3 ).
PY - 2012/6/15
Y1 - 2012/6/15
N2 - The structure and function of the human nervous system are altered in space when compared with their state on earth. To investigate directly the influence of simulated microgravity conditions which may be beneficial for cultivation and proliferation of human neural stem cells (hNSCs), the rotary cell culture system (RCCS) developed at the National Aeronautics and Space Administration (NASA) was used. RCCS allows the creation of a unique microgravity environment of low shear force, high-mass transfer and enables three-dimensional (3D) cell culture of dissimilar cell types. The results show that simulated microgravity using an RCCS would induce β-adrenoceptor, upregulate cAMP formation and activate both PKA and CREB (cAMP response element binding protein) pathways. The expression of intracellular mitochondrial genes, including PGC1α (PPAR coactivator 1α), nuclear respiratory factors 1 and 2 (NRF1 and NRF2) and mitochondrial transcription factor A (Tfam), regulated by CREB, were all significantly increased at 72. h after the onset of microgravity. Accordingly and importantly, the ATP level and amount of mitochondrial mass were also increased. These results suggest that exposure to simulated microgravity using an RCCS would induce cellular proliferation in hNSCs via an increased mitochondrial function. In addition, the RCCS bioreactor would support hNSCs growth, which may have the potential for cell replacement therapy in neurological disorders.
AB - The structure and function of the human nervous system are altered in space when compared with their state on earth. To investigate directly the influence of simulated microgravity conditions which may be beneficial for cultivation and proliferation of human neural stem cells (hNSCs), the rotary cell culture system (RCCS) developed at the National Aeronautics and Space Administration (NASA) was used. RCCS allows the creation of a unique microgravity environment of low shear force, high-mass transfer and enables three-dimensional (3D) cell culture of dissimilar cell types. The results show that simulated microgravity using an RCCS would induce β-adrenoceptor, upregulate cAMP formation and activate both PKA and CREB (cAMP response element binding protein) pathways. The expression of intracellular mitochondrial genes, including PGC1α (PPAR coactivator 1α), nuclear respiratory factors 1 and 2 (NRF1 and NRF2) and mitochondrial transcription factor A (Tfam), regulated by CREB, were all significantly increased at 72. h after the onset of microgravity. Accordingly and importantly, the ATP level and amount of mitochondrial mass were also increased. These results suggest that exposure to simulated microgravity using an RCCS would induce cellular proliferation in hNSCs via an increased mitochondrial function. In addition, the RCCS bioreactor would support hNSCs growth, which may have the potential for cell replacement therapy in neurological disorders.
KW - Human neural stem cells
KW - Mitochondrial function
KW - PGC1α
KW - Rotary cell culture system
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U2 - 10.1016/j.jneumeth.2012.04.005
DO - 10.1016/j.jneumeth.2012.04.005
M3 - Article
C2 - 22524992
AN - SCOPUS:84860336997
SN - 0165-0270
VL - 207
SP - 130
EP - 136
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
IS - 2
ER -