Isolation of Mesenchymal Stem Cells From Human Ligamentum Flavum Implicating Etiology of Ligamentum Flavum Hypertrophy
Isolation of Mesenchymal Stem Cells From Human Ligamentum Flavum Implicating Etiology of Ligamentum Flavum Hypertrophy
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DOI：
10.1097/brs.0b013e3182053f58
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发表时间：
2011-08-15
期刊：
影响因子：
3
通讯作者：
Hung, Shih-Chieh
中科院分区：
文献类型：
--
作者：
Chen, Yi-Te;Wei, Jyh-Ding;Hung, Shih-Chieh
研究设计.目的：证实黄韧带（LF）中存在间充质干细胞（MSCs），并探讨其在LF肥大中的作用。分离和表征LF衍生的MSC及其对转化生长因子-β 1（TGF-β 1）和组蛋白去乙酰化酶抑制剂（HDACi）的曲马斯他丁A（TSA）的反应。LF是一种结缔组织，其肥大变化导致椎管狭窄。TGF-β 1在椎管狭窄中的致病作用已经被牵连。TSA已显示在多种细胞中抑制TGF-β 1诱导的α-平滑肌肌动蛋白（α-SMA）、I型和III型胶原蛋白合成。MSC已从各种成人组织中分离，除了LF。LF中是否存在MSC及其对TGF-β 1和TSA的反应尚不清楚。分离并培养LF的MSCs。分析了它们的表型特征、分化潜能以及对TGF-β 1和TSA的反应。LF衍生的MSC具有与骨髓MSC相似的表面标志物特征。它们被证明具有分化为成骨细胞、脂肪细胞和软骨细胞的潜力。TGF-β 1刺激细胞增殖，增强I型和III型胶原的基因表达，并增加α-SMA的基因表达和蛋白水平。TSA可阻断TGF-β 1的致纤维化作用。目前的结果证明了从LF分离MSC。细胞对TGF-β 1的反应暗示这些细胞可能在LF肥大的发病机制中起重要作用。TSA阻断TGF-β 1的作用，可能是抑制LF肥大的有效治疗选择。
Study Design. To demonstrate the existence of mesenchymal stem cells (MSCs) in ligamentum flavum (LF) and their pathogenic role in LF hypertrophy.Objective. To isolate and characterize LF-derived MSCs and their response to transforming growth factor-beta 1 (TGF-beta 1) and trichostatin A (TSA), a histone deacetylase inhibitor (HDACi).Summary of Background Data. LF is a connective tissue, of which hypertrophic changes induce spinal stenosis. The pathogenic role of TGF-beta 1 in spinal stenosis has been implicated. TSA has been shown to suppress TGF-beta 1-induced alpha-smooth muscle actin (alpha-SMA), type I and III collagen synthesis in a variety of cells. MSCs have been isolated from a variety of adult tissues, except LF. Whether MSCs exist in LF and their response to TGF-beta 1 and TSA is not clear.Methods. The MSCs from LF were isolated and cultured. Their phenotypic character, linage differentiation potential, and response to TGF-beta 1 and TSA were analyzed.Results. LF-derived MSCs have the similar profile of surface markers as bone marrow MSCs. They were demonstrated to have the potential to be differentiated into osteoblasts, adipocytes, and chondrocytes. Administration of TGF-beta 1 stimulated cell proliferation, enhanced the gene expression of type I and III collagen, and increased the gene expression and protein level of a-SMA. TSA blocked the fibrogenic effects of TGF-beta 1.Conclusion. The current results demonstrated the isolation of MSCs from LF. The cellular response to TGF-beta 1 implied that these cells might play an important role in the pathogenesis of LF hypertrophy. TSA, which blocks the effects of TGF-beta 1, may be a potent therapeutic choice for inhibiting LF hypertrophy.