老龄化对牙周膜干细胞增殖及分化能力的影响及其机制研究

The incidence of periodontal disease increasd with age,which showed the stem cells in periodontal tissue may exist aged changes. In fact, age-related effects of stem cells have been notified in different tissues, but little is known about whether PDLSCs exhibit different features, The influences of aging on the MSC properties of PDLSCs remain unidentified, which, however, may have significant effects on final clinical.outcomes because tissue regenerative potential may be negatively regulated by aging.What the effects of these changes on the characteristics of periodontal ligament stem cells(PDLSCs) and the clinical transformation application, what are these mechanisms, how to forecast, how to cope with the possible influences, are to be solved in the process of clinical transformation of PDLSCs urgently. Our previous studies have found that PDLSCs from different age sources showed different biological characteristics. The research on the effects of aging on the charactiristics of PDLSCs will be done. The research will be conducted from two aspects : in vitro and in vivo on the effects of agine on proliferation and multi-directional differentiation capacity and influence on periodontal tissue regeneration of the PDLSCs. Meanwhile , the influence of the outside environment of PDLSCs from different ages on PDLSCs characteristics will be observed. By the epigenetics methods, we will try to screen the age-related epigenetics enzyme, and to control the target enzyme, to improve the proliferation and differentiation abilities of aging PDLSCs and preliminary explore the possibility of the reversion of the aging PDLSCs and mechanisms. The research has the vital significance to further understand the mechanism of PDLSCs in periodontal tissue regeneration and look for clinical therapeutic targets and new treatment. Meanwhile it is significant for the application of clinical translational medicine of PDLSCs, providing data that may help for case or cell source selection in future clinical trials onstem cell-based periodontal therapeutics.

牙周病发病率随着年龄的增长逐渐增加，说明牙周组织中的干细胞可能存在增龄性变化，这种增龄性变化对牙周膜干细胞（periodontal ligament stem cells，PDLSCs）特性及其临床转化应用如何影响，机制如何，都是PDLSCs临床转化过程中亟待解决的问题。前期研究发现，不同年龄来源的PDLSCs的生物学特性确有差异，提示老龄化对PDLSCs的特性及临床应用有着重要的影响。拟对PDLSCs的增龄性改变特征及其在牙周组织再生中的作用进行研究，从体外和体内两个方面研究PDLSCs在增龄情况下的增殖、多向分化能力及其对牙周组织再生的影响，观察外环境对不同年龄段PDLSCs活性和干性的影响，利用表观遗传学方法筛选衰老相关酶，调控目标酶，改善老龄PDLSCs的干性，初步探讨PDLSCs老化及逆转的可能性及机制。

牙周病发病率随着年龄的增长逐渐增加，说明牙周组织中的干细胞可能存在增龄性变化，这种增龄性变化对牙周膜干细胞（periodontal ligament stem cells，PDLSCs）特性及其临床转化应用如何影响，机制如何，都是PDLSCs临床转化过程中亟待解决的问题。前期研究发现，不同年龄来源的PDLSCs的生物学特性确有差异，提示老龄化对PDLSCs的特性及临床应用有着重要的影响。本研究对PDLSCs的增龄性改变特征及其在牙周组织再生中的作用进行研究，研究PDLSCs在增龄情况下的增殖、多向分化能力及其对牙周组织再生的影响，观察外环境等处理因素对不同年龄段PDLSCs活性和干性的影响，进而通过比较不同年龄干细胞的免疫调控能力，探索了未来干细胞用于临床所面临的免疫问题，研究结果表明：PDLSCs随着来源者年龄的增长（均衡性别和其它混杂因素后），其增殖能力、克隆形成能力、成骨分化能力等出现增龄性的下降趋势，使用天然多酚类物质白藜芦醇预处理PDLSCs，可提升老年PDLSCs增殖及成骨能力，年轻骨髓间充质干细胞调控巨噬细胞向M2方向诱导的能力强于年老骨髓间充质干细胞。本项目通过深入研究，为改善老龄PDLSCs的干性、逆转老化PDLSCs及干细胞的临床应用的免疫调控提供了理论依据，具有很好的基础和临床应用前景。