Mechanism of Hyaluronan on the Regulation of the Mitochondrial Function of Human Placenta-Derived Mesenchymal Stem Cells

• Main Authors: Mairim Alexandra SolisTejada, 梅琳恩
• Other Authors: Lynn L.H. Huang
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/gnb7k7

博士 === 國立成功大學 === 生物科技研究所 === 104 === Hyaluronan preserves the proliferation and differentiation potential of mesenchymal stem cells by controlling cell cycle transit and proliferation rate. Human placenta-derived mesenchymal stem cells (PDMSCs) cultured on suspension hyaluronan (SHA) at low concentrations enhances proliferation rate, whereas cultured on coated hyaluronan (CHA) reduces cell proliferation. Nonetheless, the molecular mechanism of this event was not yet underscored. Mitochondria are known to play a crucial role in stem cell self-renewal and differentiation. Thus, in this study we aimed to investigate the metabolic mechanism underlying the hyaluronan-regulated proliferative maintenance of stem cells by evaluating mitochondrial functions. Results showed that hyaluronan increased mitochondrial biogenesis and function, and reduced reactive oxygen species levels. Fast proliferative PDMSCs on SHA, when compared to slow-proliferative PDMSCs on CHA, showed an increase in lactate production and ATP content with reduced mitochondrial oxygen consumption rate (OCR). However, increasing concentrations of hyaluronan in CHA upregulated the expression of mitochondrial biogenesis-related genes PGC1-α and mTFA; increased mitochondrial biogenesis; and favored mitochondrial function with an increase of MMP, OCR, and ATP. Although hyaluronan seemed to favor mitochondrial function, cell entry into a hyaluronan-regulated slow-proliferative mode led to a 5-fold reduction in ATP production and coupling efficiency levels. Together, these results suggest that hyaluronan influences the proliferative state of PDMSCs by favoring mitochondrial function. A clear understanding of the metabolic mechanism induced by hyaluronan in stem cells will allow future applications that may overcome the current limitations faced in stem cell culture.