Browsing by Author "Chen, Ming-Hong"

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Dose-dependent regulation of cell proliferation and collagen degradation by estradiol on ligamentum flavum
(2014-07-15)
Chen, Mei-Hsiu
;
Hu, Chao-Kai
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Chen, Pei-Ru
;
Chen, Yu-Shan
;
Sun, Jui-Sheng
Background: Estradiol plays an important role in the regulation of collagen metabolism. Deficiency of estradiol has been reported to be associated with the degeneration of many connective tissues. However, the association of estradiol and hypertrophy of the ligamentum flavum was seldom explored. Therefore, we studied the effects of estradiol on cultured cells from the ligamentum flavum. Methods: Primary cultures of human ligamentum flavum cells obtained from surgical specimens of 14 patients undergoing spinal surgery were used to investigate the effect of estradiol on cell proliferation and the expression of collagen, elastin, and matrix metalloproteinases. Downstream pathways of estrogen receptor underlying the regulation of metalloproteinases were also investigated. Results: In our study, we revealed the existence of estrogen receptors on both female and male ligamentum flavum cells with a gender difference. 17 beta-estradiol increased early (24 hours) proliferation of ligamentum flavum cells in a dose dependent manner and the effect could not be seen when the cell density increased. Estradiol with a concentration of 10-9 M decreased collagen levels and increased the expression of MMP-13. Adding an antagonist of PI3K downstream pathway could reverse the expression of MMP-13 caused by estradiol. Conclusions: The results implied estradiol regulated the expression of MMP-13 via PI3K pathway and contributed to the homeostasis of extracellular matrix in the ligamentum flavum.
Glycosaminoglycan-based hybrid hydrogel encapsulated with polyelectrolyte complex nanoparticles for endogenous stem cell regulation in central nervous system regeneration
(2018-08-01)
Jian, Wei-Hong
;
Wang, Huan-Chih
;
Kuan, Chen-Hsiang
;
Chen, Ming-Hong
;
Wu, Hsi-Chin
The poor regenerative capability of stem cell transplantation in the central nervous system limits their therapeutic efficacy in brain injuries. The sustained inflammatory response, lack of structural support, and trophic factors deficiency restrain the integration and long-term survival of stem cells. Instead of exogenous stem cell therapy, here we described the synthesis of nanohybrid hydrogel containing sulfated glycosaminoglycan-based polyelectrolyte complex nanoparticles (PCN) to mimic the brain extracellular matrix and control the delivery of stromal-derived factor-1 alpha (SDF-1 alpha) and basic fibroblast factor (bFGF) in response to matrix metalloproteinase (MMP) for recruiting endogenous neural stem cells (NSC) and regulating their cellular fate. Bioactive factors are delivered by electrostatic sequestration on PCN to amplify the signaling of SDF-1 alpha and bFGF to regulate NSC in vitro. In in vivo ischemic stroke model, the factors promoted neurological behavior recovery by enhancing neurogenesis and angiogenesis. These combined strategies may be applied for other tissue regenerations by regulating endogenous progenitors through the delivery of different kinds of glycosaminoglycan-binding molecules. (C) 2018 Elsevier Ltd. All rights reserved.