Overexpression of PGC-1α in Human Bone Marrow Stem Cells: the Regulation of Mitochondria and the Inhibition of Growth Rate

• Main Authors: Li-Hsin Chen, 陳立欣
• Other Authors: Hung-Hai Ku
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/24620280621612257395

碩士 === 國立陽明大學 === 解剖暨細胞生物學研究所 === 94 === Stem cells have a unique “self-renewal” ability. This enables them to continuously divide throughout the life of the organism and to maintain their pluripotency without aging. On the other hand, it has been reported that mitochondrion plays an important role in regulating cellular life span and cellular senescence. Mitochondria are few and small in human embryonic stem cells. In addition, PGC-1α belongs to a family of coactivator. It has been proved to regulate energy metabolism and increase mitochondrial mass in many cell types. In order to investigate if stem cells would alter their quiescent status by increasing mitochondrial mass, human bone marrow stem cells (BMSCs) were isolated and PGC-1α was overexpressed in these cells through adenoviral expression system. It was found that overexpression of PGC-1α do increase mitochondrial mass by two times in BMSCs. As compared to the control, the doubling time increased 3 folds after BMSCs were infected by PGC-1α incorporated adenovirus. The percentages of expressing senescence-associated β-galactosidase (SA-β-Gal) activity were significantly increased to 40% in Day 7 overexpressed PGC-1α BMSCs as compared to 7% in control. Moreover, ROS production in overexpressed PGC-1α BMSCs was doubled as compared to those in BMSCs infected by vector only. In conclusion, these results suggested that by increasing mitochondrial mass via adenoviral-mediated expression of PGC-1α, a reduction in cell growth and cellular senescence could be induced in BMSCs. Therefore, mitochondria play a critical role in regulating cellular life span.