Beta-adrenoceptor pathway enhances mitochondrial function in human neural stem cells via rotary cell culture system

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• 作者：Ming-Chang Chiang^a ; ^{cmcphd@gmail.com} ; Heng Lin^b ; Yi-Chuan Cheng^c ; Chia-Hui Yen^d ; Rong-Nan Huang^e ; Kuan-Hung Lin^f
• 关键词：Rotary cell culture system ; Human neural stem cells ; PGC1伪 ; Mitochondrial function
• 刊名：Journal of Neuroscience Methods
• 出版年：2012
• 期刊代码：33_01650270
• 类别：neu
• 出版时间：15 June, 2012
• 卷：207
• 期：2
• 页码：130-136
• 文件大小：736 K

摘要

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 尾-adrenoceptor, upregulate cAMP formation and activate both PKA and CREB (cAMP response element binding protein) pathways. The expression of intracellular mitochondrial genes, including PGC1伪 (PPAR coactivator 1伪), 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.