Dental Stem Cells and Tooth Tissue Engineering

描述（由申请人提供）：我们的长期目标是确定可用于人类自体牙齿组织工程的细胞群和方法。识别和操纵成体牙齿干细胞（DSCs）的能力将大大促进这一过程。虽然相当多的文献支持上皮和间充质干细胞的存在，但相对于其他干细胞，包括神经干细胞、骨髓基质干细胞、造血干细胞、精原干细胞和角质形成细胞，干细胞本身的特征仍然很差。特别是，目前缺乏可用于产生富集的DSC群体、鉴定成人DSC群体和检查非牙齿组织中牙源性潜能诱导的工具，例如DSC表面标记物的抗体。我们假设，出生后的牙齿干细胞（DSCs）的鉴定和表征，结合最先进的组织工程技术，将促进整个牙齿组织工程的努力。我们最近的牙齿组织工程结果表明，我们有能力分离和维持培养，上皮和间充质出生后的DSCs，并使用这些细胞的生物工程含有牙本质和釉质的小牙冠。基于这些有希望的初步结果，在这里，我们提出了研究，其成功完成将定义生物工程牙齿的预定大小和形状的方法。我们建议：1）使用充分表征的干细胞分选技术建立和表征富集的上皮和间充质DSC群体，并使用我们的功能性牙齿组织工程测定来确认它们的身份;以及2）定义支架材料和设计，用于优化特定尺寸和形状的牙齿组织的生物工程。成功完成拟议的目标将显着提高我们的知识和理解的DSCs及其在牙齿组织工程的潜在效用，并将提供最终的自体牙齿组织工程在人类的基础。

DESCRIPTION (provided by applicant): Our long-term goal is to define cell populations and methods that can be used for autologous tooth tissue engineering in humans. The ability to identify and manipulate adult dental stem cells (DSCs) would significantly facilitate this process. Although a considerable body of literature supports the existence of epithelial and mesenchymal DSCs, DSCs themselves remain poorly characterized relative to other stem cells including neural, bone marrow stromal, hematopoetic, spermatogonial and keratinocyte stem cells. In particular, tools such as antibodies to DSC surface markers that could be used to generate enriched DSC populations, to identify adult DSC populations, and to examine the induction of odontogenic potential in non-dental tissues, are currently lacking. We hypothesize that the identification and characterization of post-natal dental stem cell (DSCs), combined with state-of the art tissue engineering techniques, will facilitate whole tooth tissue engineering efforts. Our recent tooth tissue engineering results demonstrate our ability to isolate, and maintain in culture, epithelial and mesenchymal post-natal DSCs, and to use these cells to bioengineer small tooth crowns containing dentin and enamel. Based on these promising initial results, here we propose studies whose successful completion will define methods to bioengineer teeth of predetermined size and shape. We propose: 1) to establish and characterize enriched epithelial and mesenchymal DSC populations using well-characterized stem cell sorting techniques, and to confirm their identity using our functional tooth tissue-engineering assay; and 2) to define scaffold materials and design for optimized bioengineering of tooth tissues of specified size and shape. The successful completion of the proposed aims will significantly improve our knowledge and understanding of DSCs and their potential utility in tooth tissue engineering, and will provide the foundation for eventual autologous tooth tissue engineering in humans.