Polarization of dental pulp stem cells

牙髓干细胞的极化

• 批准号: 10039689
• 负责人: Xiaohua Liu
• 金额: $ 22.69万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10039689
• 关键词: 3-Dimensional; Ablation; Animals; Architecture; Award; BMP2 gene; Biochemical; Biocompatible Materials; Biological Process; Biology; Biomedical Engineering; Biomimetic Materials; Biomimetics; Biophysics; Cell Communication; Cell physiology; Cells; Cellular Morphology; Centrosome; Dental; Dental Pulp; Dentin; Dentin Formation; Development; Endodontics; Environment; Extracellular Matrix; Future; Gelatin; Gene Expression Profile; Goals; Golgi Apparatus; Growth Factor; Health; In Situ; In Vitro; Knowledge; Lasers; Location; Mandible; Minerals; Miniature Swine; Morphology; Natural regeneration; Neurons; Nutrient; Odontoblasts; Odontogenesis; Outcome; Pilot Projects; Process; Proteins; Research; Signal Transduction; Structure; Surface; Technology; Tissue Engineering; Tissues; Tooth structure; Transforming Growth Factors; Tubular formation; Work; base; bone; cell type; design; high risk; improved; innovation; migration; nanofabrication; nanofiber; polarized cell; regenerative; rho GTP-Binding Proteins; scaffold; stem cells; tool; transcriptome; transcriptome sequencing

Project Summary Cell polarization is a fundamental feature of many cell types that display specialized morphologies to perform distinct functions. Odontoblasts are a type of highly polarized dental cells with a high secretory function to form dentin that is a major component of a tooth. The polarization of odontoblasts is a prerequisite for the formation of dentin with tubular structure that is crucial for maintaining the normal biological functions of a tooth. Many studies have shown that dental pulp stem cells (DPSCs) can be polarized and differentiated into odontoblast-like cells. However, the factors that control DPSC polarization and the underlying mechanism remain unknown. Because of that, most of tissue engineering approaches for regenerative endodontics only regenerated non-tubular bone-like mineralized tissues. The main obstacle to explore DPSC polarization is the lack of a bio- inspired three-dimensional (3D) “clean” platform that is capable of deciphering the biophysical and biochemical signals that initiate and regulate DPSC polarization. Recently, we developed a bio-inspired tubular 3D matrix and successfully regenerated highly organized tubular dentin. Furthermore, we identified that the tubular architecture of the synthetic matrix is a crucial biophysical factor to initiate DPSC polarization and form tubular dentin. In our pilot study, we have further developed a unique micropatterning and laser ablation technology to create a bio-inspired 3D “clean” platform that can precisely manipulate one single cell (or multiple cells) in a microisland of the 3D platform, therefore, is capable of deciphering the signals that initiate/regulate DPSC polarization. The proposed project, therefore, is to use the unique “clean” 3D platform to identify and analyze the biophysical and biochemical factors that control DPSC polarization. We hypothesize that DPSC polarization is initiated by a set of biophysical and biochemical factors that work synergistically to regulate and stabilize the polarized DPSCs. To accomplish the overall objective for this project, the following two aims are proposed: Aim 1 is to identify biophysical factors that initiate and modulate DPSC polarization; and Aim 2 is to identify biochemical factors that regulate DPSC polarization. Successfully completing this work will fundamentally advance the understanding of DPSC polarization and greatly promote the ability to develop new bio-inspired matrices for regenerative endodontics.

项目摘要 细胞极化是许多细胞类型的基本特征，这些细胞类型显示出专门的形态 执行不同的功能。 Odontoblasts是一种高度极化的牙科细胞，具有高秘密功能 形成牙本，这是牙齿的主要组成部分。 Odontoblasts的两极分化是 牙本质与管状结构的形成对于维持牙齿的正常生物学功能至关重要。 许多研究表明，牙髓干细胞（DPSC）可以极化并分化为 Odontoblast样细胞。但是，控制DPSC极化和潜在机制的因素仍然存在 未知。因此，大多数的组织工程方法用于再生牙髓牙齿牙齿牙齿牙齿牙齿牙齿牙齿的再生 非管状骨状矿化组织。探索DPSC极化的主要障碍是缺乏生物 启发的三维（3D）“清洁”平台，能够破译生物物理和生化 启动和调节DPSC极化的信号。最近，我们开发了一个由生物启发的管状3D矩阵 并成功再生高度组织的管状牙本质。此外，我们确定了管状 合成基质的结构是启动DPSC极化并形成管状的至关重要的生物物理因子 牙本质。在我们的试点研究中，我们进一步开发了一种独特的微图案和激光消融技术 创建一个由生物启发的3D“清洁”平台，可以精确操纵一个单元（或多个单元格） 因此，3D平台的微岛能够破译启动/调节DPSC的信号 极化。因此，拟议的项目是使用独特的“清洁” 3D平台来识别和分析 控制DPSC极化的生物物理和生化因子。我们假设DPSC极化是 由一组生物物理和生化因素引发的，它们协同调节和稳定 极化DPSC。为了实现该项目的总体目标，提出了以下两个目标：目标 1是确定启动和调节DPSC极化的生物物理因子；目标2是确定 调节DPSC极化的生化因子。成功完成这项工作将从根本上 促进对DPSC两极化的理解，并大大促进发展新生物启发的能力 再生牙齿牙齿的矩阵。