Browsing by Author "Sun, Li-Yi"

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Butylidenephthalide Suppresses Human Telomerase Reverse Transcriptase (TERT) in Human Glioblastomas
(2011-11-01)
Lin, Po-Cheng
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Lin, Shinn-Zong
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Chen, Yi-Lin
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Chang, Jeng-Shou
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Ho, Li-Ing
Telomerase is widely expressed in most human cancers, but is almost undetectable in normal somatic cells and is therefore a potential drug target. Using the human telomerase promoter platform, the naturally occurring compound butylidenephthalide (BP) was selected for subsequent investigation of antitumor activity in vitro and in vivo. We treated human glioblastoma cells with BP and found a dose-dependent decrease in human telomerase reverse transcriptase (hTERT) mRNA expression and a concomitant increase in p16 and p21 expression. Because c-Myc and Sp1 are involved in transcriptional regulation of hTERT, the effect of BP on c-Myc and Sp1 expression was examined. Using electrophoretic mobility shift assays and western blotting, we showed that BP represses hTERT transcriptional activity via downregulation of Sp1 expression. Using the telomerase repeat amplification protocol, an association between BP concentration and suppression of telomerase activity, induction of human glioblastoma senescence, and inhibition of cellular proliferation was identified. This was supported by a mouse xenograft model, in which BP repressed telomerase and inhibited tumor proliferation, resulting in tumor senescence. Overexpression of hTERT restored telomerase activity in human glioblastoma cells and overcame replicative senescence. These findings suggest that BP inhibits proliferation and induces senescence in human glioblastomas by downregulating hTERT expression and consequently telomerase activity. This is the first study to describe regulation of telomerase activity by BP in human glioblastomas.
Effect of Pulsed Electromagnetic Field on the Proliferation and Differentiation Potential of Human Bone Marrow Mesenchymal Stem Cells
(2009-05-01)
Sun, Li-Yi
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Hsieh, Dean-Kuo
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Yu, Tzai-Chiu
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Chiu, Hsien-Tai
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Lu, Sheng-Fen
Pulsed electromagnetic fields (PEMFs) have been used clinically to slow down osteoporosis and accelerate the healing of bone fractures for many years. The aim of this study is to investigate the effect of PEMFs on the proliferation and differentiation potential of human bone marrow mesenchymal stem cells (BMMSC). PEMF stimulus was administered to BMMSCs for 8 h per day during culture period. The PEMF applied consisted of 4.5 ms bursts repeating at 15 Hz, and each burst contained 20 Pulses. Results showed that about 59% and 40% more viable BMMSC cells were obtained in the 2 PEMF-exposed Cultures at 24 h after plating for the seeding density of 1000 and 3000 cells/cm(2) respectively. Although, based on the kinetic analysis, the growth rates of BMMSC during the exponential growth phase were not significantly affected, 20-60% higher cell densities were achieved during the exponentially expanding stage. Many newly divided cells appeared from 12 to 16 h after the PEMF treatment as revealed by the cell cycle analysis. These results Suggest that PEMF exposure Could enhance the BMMSC cell proliferation during the exponential phase and it possibly resulted from the shortening of the lag phase. In addition, according to the cytochemical and immunofluorescence analysis performed, the PEMF-exposed BMMSC showed multi-lineage differentiation potential similar to the control group. Bioelectromagnetics 30:251-260, 2009. (C) 2009 Wiley-Liss. Inc.
Functional Cells Cultured on Microcarriers for Use in Regenerative Medicine Research
(2011-01-01)
Sun, Li-Yi
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Lin, Shinn-Zong
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Li, Yuan-Sheng
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Harn, Horng-Jyh
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Chiou, Tzyy-Wen
Microcarriers have been successfully used for many years for growing anchorage-dependent cells and as a means of delivering cells for tissue repair. When cultured on microcarriers, the number of anchorage-dependent cells, including primary cells, can easily be scaled up and controlled to generate the quantities of cells necessary for therapeutic applications. Recently, stem cell technology has been recognized as a powerful tool in regenerative medicine, but adequate numbers of stem cells that retain their differentiation potential are still difficult to obtain. For anchorage-dependent stem cells, however, microcarrier-based suspension culture using various types of microcarriers has proven to be a good alternative for effective ex vivo expansion. In this article, we review studies reporting the expansion, differentiation, or transplantation of functional anchorage-dependent cells that were expanded with the microcarrier culture system. Thus, the implementation of technological advances in biodegradable microcarriers, the bead-to-bead transfer process, and appropriate stem cell media may soon foster the ability to produce the numbers of stem cells necessary for cell-based therapies and/or tissue engineering.
Pulsed Electromagnetic Fields Accelerate Proliferation and Osteogenic Gene Expression in Human Bone Marrow Mesenchymal Stem Cells During Osteogenic Differentiation
(2010-04-01)
Sun, Li-Yi
;
Hsieh, Dean-Kuo
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Lin, Po-Cheng
;
Chiu, Hsien-Tai
;
Chiou, Tzyy-Wen
Osteogenesis is a complex series of events involving the differentiation of mesenchymal stem cells to generate new bone. In this study, we examined the effect of pulsed electromagnetic fields (PEMFs) on cell proliferation, alkaline phosphatase (ALP) activity, mineralization of the extracellular matrix, and gene expression in bone marrow mesenchymal stem cells (BMMSCs) during osteogenic differentiation. Exposure of BMMISCs to PEMFs increased cell proliferation by 29.6% compared to untreated cells at day 1 of differentiation. Semi-quantitative RT-PCR indicated that PEMFs significantly altered temporal expression of osteogenesis-related genes, including a 2.7-fold increase in expression of the key osteogenesis regulatory gene cbfa1, compared to untreated controls. In addition, exposure to PEMFs significantly increased ALP expression during the early stages of osteogenesis and substantially enhanced mineralization near the midpoint of osteogenesis. These results suggest that PEMFs enhance early cell proliferation in B M MSC-mediated osteogenesis, and accelerate the osteogenesis. Bioelectromatmetics 31:209-219, 2010. (C) 2009 Wiley-Liss, Inc.