牙髓细胞（DPCs）是牙再生重要的种子细胞，诱导其重编程，并应用于组织再生，在口腔再生医学中具备良好的应用前景。成体细胞导入转录因子可重编程为诱导性多能干细胞（iPSCs）。BMP-4/Smad1信号位于重编程网络Oct-4、Sox2、Nanog上游，与其整合调控细胞重编程能力，但对DPCs重编程的调控作用尚未明确。本课题组前期研究发现鼠胚胎成纤维细胞（MEF）可分泌BMP-4和Smad1，调节细胞培养微环境，显著提高DPCs重编程能力。本项目拟进一步探讨细胞培养微环境诱导DPCs重编程的作用机制，采用液体芯片鉴定MEF改性微环境的活性分子对诱导DPCs重编程的调控作用，构建非病毒转染DPCs来源iPSCs模型，研究其在牙再生中的应用，阐明BMP-4/Smad1信号在DPCs重编程中的调节机制，为实现牙再生提供实验依据。

Dental pulp cells (DPCs) are of great importance to dental regeneration, thus application of DPCs with optimized reprogramming ability to tissue engineering is the cutting edge of dental regeneration medicine. Somatic cells can be induced to induced pluripotent stem cells (iPSCs) with the transfection of transcriptional factors. BMP-4/Smad1 locating at the upstream of the reprogramming network (Oct-4, Sox2 and Nanog), cooperates with which to modulate reprogramming, albeit its mechanism modulating reprogramming of DPCs remains unknown. Our previous studies demonstrated that mouse embryonic fibroblasts (MEF) enhanced the cell reprogramming property of DPCs through upregulating BMP-4 and Smad1. Therefore, the present study is to identify the molecules modulating cell programming property of DPCs through cell-cell communication with MEF, and investigate the mechanism underlying cell reprogramming of DPCs to iPSCs without virus tranfection, which will be of critical importance to the appliction of DPCs to dental regeneration.