异体牙周膜干细胞与NK细胞相互作用及机制研究

Defects of teeth and periodontal tissues have a high incidence in all regions of the world and their subsequent dysfunction affect human health and quality of life seriously. Periodontal ligament stem cells （PDLSCs）are the best seed cells resource for regeneration of teeth and periodontal tissue with a booming clinical application. However, autologous periodontal ligament stem cells are limited in the patients. If PDLSCs can be used in allogeneic transplantation, the source of seed cells can be expanded greatly which will greatly promote the restoration of lost teeth and regeneration of periodontal tissue. Whether allogeneic transplantation of PDLSCs has allograft immune rejection is one of the key issue to be solved. Human immunity included innate immunity and adaptive immunity. Our previous studies have proved that PDLSCs possessed immunosuppressive function in adaptive immunity including cellular immunity and humoral immunity. But there is no report about the interaction between the allogeneic PDLSCs and innate immunity, and NK cells play the key role in innate immunity. In this study, we will investigate whether allogeneic PDLSCs affect the functions of NK cell, such as cell proliferation, antibody-dependent cell-mediated cytoxicity and secretion function, and whether NK cells affect the function of allogeneic PDLSCs on their phenotype, differentiation potentials, etc. Further study will also carry on to explore interactional mechanisms. Through our study, we will elucidate the interactional characteristics and mechanism between allogeneic PDLSCs and NK cells, and provide scientific basis for allogeneic PDLSC-mediated the regeneration of teeth and periodontal tissue in clinic.

牙齿及牙周组织缺损、缺失严重影响人类身心健康，目前，干细胞介导的牙齿及牙周组织再生是口腔医学研究的热点。研究表明牙周膜干细胞是牙齿及牙周组织再生的最佳种子细胞之一，但自体牙周膜干细胞来源有限，如能异体应用,则能扩展种子细胞的来源；但异体应用是否具有免疫排斥是亟需解决的关键科学问题之一。机体免疫分为固有免疫和适应性免疫,本课题组前期研究发现异体牙周膜干细胞具有调节机体适应性免疫的能力,但固有免疫与异体牙周膜干细胞之间的相互作用尚不明确。NK细胞在固有免疫反应中起主要作用，本课题拟在前期工作基础上，进一步研究异体牙周膜干细胞与NK细胞的相互作用，观察其对NK细胞增殖、毒性、分泌等功能的影响，同时研究NK细胞对牙周膜干细胞表型、分化等功能的影响，并深入探讨其相互作用的分子机制。通过本研究可以阐明异体牙周膜干细胞与NK细胞之间相互作用特点和机制，为异体牙周膜干细胞再生牙齿和牙周组织提供科学依据。

牙齿及牙周组织缺损、缺失严重影响人类身心健康，目前，干细胞介导的牙齿及牙周组织再生是口腔医学研究的热点。研究表明牙髓干细胞是牙齿及牙周组织再生的最佳种子细胞之一，但自体牙髓干细胞来源有限，如能异体应用,则能扩展种子细胞的来源；但异体应用是否具有免疫排斥是亟需解决的关键科学问题之一。机体免疫分为固有免疫和适应性免疫,本课题组前期研究发现异体牙周膜干细胞具有调节机体适应性免疫的能力,但固有免疫与异体牙髓干细胞（hPDLSCs）之间的相互作用尚不明确。NK 细胞在固有免疫反应中起主要作用，本课题拟在前期工作基础上，进一步研究异体牙髓干细胞与 NK 细胞的相互作用，观察其对 NK 细胞增殖、毒性、分泌等功能的影响。通过本研究可以阐明异体牙髓干细胞与 NK 细胞之间相互作用特点和机制，为异体牙髓干细胞再生牙齿和牙周组织提供科学依据。. 通过本实验发现，hDPSCs以及人骨髓干细胞(hBMSCs)均可以有效的抑制同种异体NK细胞的增殖能力，而且这种抑制作用是剂量依赖性的；hDPSCs和hBMSCs可有效的抑制NK细胞的杀伤功能功能；hDPSCs和hBMSCs对NK细胞的凋亡无明显影响；在hDPSCs和hBMSCs的作用下，NK细胞获得CD73表达，通过CD39和CD73的协同作用，ATP被分解产生大量的腺苷，腺苷继而通过自分泌作用抑制NK细胞功能