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衰老的人牙周膜干细胞增殖和分化能力的丧失以及通过暴露于年轻的外部环境实现年轻化。

Loss of proliferation and differentiation capacity of aged human periodontal ligament stem cells and rejuvenation by exposure to the young extrinsic environment.

作者信息

Zheng Wei, Wang Shi, Ma Dandan, Tang Liang, Duan Yinzhong, Jin Yan

机构信息

Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.

出版信息

Tissue Eng Part A. 2009 Sep;15(9):2363-71. doi: 10.1089/ten.tea.2008.0562.

DOI:10.1089/ten.tea.2008.0562
PMID:19239403
Abstract

The application of periodontal ligament stem cells (PDLSCs) may be effective for periodontal regenerative therapy. As tissue regenerative potential may be negatively regulated by aging, whether aging and its microenvironment modify human PDLSCs remains a question. In this study, we compared the proliferation and differentiation capacity of PDLSCs obtained from young and aged donors. Then, we exposed aged PDLSCs to young periodontal ligament cell-conditioned medium (PLC-CM), and young PDLSCs were exposed to aged PLC-CM. Morphological appearance, colony-forming assay, cell cycle analysis, osteogenic and adipogenic induction media, gene expression of cementoblast phenotype, and in vivo differentiation capacities of PDLSCs were evaluated. PDLSCs obtained from aged donors exhibited decreased proliferation and differentiation capacity when compared with those from young donors. Young PLC-CM enhanced the proliferation and differentiation capacity of PDLSCs from aged donors. Aged PDLSCs induced by young PLC-CM showed enhanced tissue-regenerative capacity to produce cementum/periodontal ligament-like structures, whereas young PDLSCs induced by aged PLC-CM transplants mainly formed connective tissues. To our knowledge, this is the first study to mimic the developmental microenvironment of PDLSCs in vitro, and our data suggest that age influences the proliferation and differentiation potential of human PDLSCs, and that the activity of human PDLSCs can be modulated by the extrinsic microenvironment.

摘要

牙周膜干细胞(PDLSCs)的应用可能对牙周再生治疗有效。由于组织再生潜力可能会受到衰老的负面影响,衰老及其微环境是否会改变人牙周膜干细胞仍是一个问题。在本研究中,我们比较了从年轻和老年供体获得的牙周膜干细胞的增殖和分化能力。然后,我们将老年牙周膜干细胞暴露于年轻牙周膜细胞条件培养基(PLC-CM)中,而年轻牙周膜干细胞则暴露于老年PLC-CM中。评估了牙周膜干细胞的形态外观、集落形成试验、细胞周期分析、成骨和成脂诱导培养基、成牙骨质细胞表型的基因表达以及体内分化能力。与年轻供体来源的牙周膜干细胞相比,老年供体来源的牙周膜干细胞增殖和分化能力下降。年轻的PLC-CM增强了老年供体来源的牙周膜干细胞的增殖和分化能力。由年轻PLC-CM诱导的老年牙周膜干细胞显示出增强的组织再生能力,能够产生牙骨质/牙周膜样结构,而由老年PLC-CM移植诱导的年轻牙周膜干细胞主要形成结缔组织。据我们所知,这是第一项在体外模拟牙周膜干细胞发育微环境的研究,我们的数据表明年龄会影响人牙周膜干细胞的增殖和分化潜能,并且人牙周膜干细胞的活性可以被外在微环境调节。

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