Postnatal Stem Cell-Mediated Tooth Regeneration

产后干细胞介导的牙齿再生

• 批准号: 7619612
• 负责人: SONGTAO SHI
• 金额: $ 23.23万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-05 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7619612
• 关键词: Absorbable Gelatin Sponge; Adipocytes; Animal Model; Apical; Arts; Autologous; Biological; Cell Count; Cells; Characteristics; Chondrocytes; Clinical; Complex; Data; Dental; Dental Implantation; Dental Implants; Dental Porcelain; Dental Pulp; Dental crowns; Dentin; Dentin Formation; Development; Edentulous Mouth; Future; Gene Expression Profile; Goals; Human; Hydroxyapatites; Immunocompromised Host; Implant; Implantation procedure; In Vitro; Label; Lead; Mandible; Mediating; Miniature Swine; Modeling; Molecular; Multipotent Stem Cells; Mus; Natural regeneration; Neurons; Periodontal Ligament; Peroxisome Proliferator-Activated Receptors; Plant Roots; Population; Pre-Clinical Model; Property; Publishing; Shapes; Specific qualifier value; Stem cell transplant; Stem cells; Structure; Telomerase; Tissues; Tooth structure; Translating; Transplantation; clinical application; human stem cells; improved; in vivo; lipoprotein lipase; novel; novel strategies; oil red O; orofacial; postnatal; progenitor; scaffold; stem; stem cell population; stem cell technology; tissue regeneration; tongue papilla; translational approach

DESCRIPTION (provided by applicant): The objective of this application is to further characterize newly identified Stem Cells derived from root Apical Papilla (SCAP) and explore the potentiality of using SCAP along with periodontal ligament stem cells (PDLSCs) to regenerate root/periodontal tissue in the edentulous region by regular clinical dental implant procedures in a minipig model. We have recently isolated human SCAP and found their distinct properties from other dental stem cells such as dental pulp stem cells (DPSCs). In particular, SCAP show an increased dentin regeneration capacity in vivo, a distinct gene expression profile, and detectable levels of telomerase activity. Our preliminary studies imply that SCAP are early stem progenitors responsible for root formation, suggesting that SCAP may have advantages to be utilized for dental tissue regeneration. Before SCAP are considered for any clinical application, it is critical to understand their stem cell properties in depth. Very recently, we published part of our preliminary data to demonstrate that autologous SCAP and PDLSCs are capable of generating root/periodontal ligament tissues in the socket of newly extracted tooth to serve as a supporter to install porcelain crown in minipigs. However, this early "proof of principle" evidence does not represent regular clinical implant procedures. Therefore, we propose to explore potential of using SCAP and PDLSCs to regenerate root/periodontal tissues in the edentulous region mimicking clinical dental implant therapies. This approach may provide critical evidence for potential clinical application in the future. In this application, we will characterize multipotent differentiation of human and minipig SCAP and then utilize minipig SCAP and PDLSCs, a stem cell population capable of forming periodontal tissue, to cooperatively regenerate root/PDL complex. The reason of selecting minipigs for root/periodontal tissue regeneration is due to their similarity to humans in terms of their orofacial tissue structures and characteristics of dental stem cells. We will use molecular, cellular, histological, immunological, and stem cell transplantation approaches to characterize human SCAP and minipig SCAP/PDLSCs. The final goal of this proposed study is to explore potential of utilizing two populations of dental stem cells to reconstruct biologic root/periodontal complex in a pre-clinical model. We anticipate that our proposed studies in this R21 application will lead to a R01 application in the future.

描述（由申请人提供）：本应用的目的是进一步表征源自根顶乳头（SCAP）的新鉴定的干细胞，并探讨使用SCAP以及牙周韧带干细胞（PDLSCS）在Minipig模型中通过常规的临床牙科植入植入手术在肾上腺牙本质中再生根/牙周组织的潜力。我们最近分离了人类SCAP，并发现了它们与其他牙科干细胞（例如牙髓干细胞（DPSC））的独特特性。特别是，SCAP在体内显示出牙本质再生能力的增加，这是一个独特的基因表达谱以及可检测的端粒酶活性水平。我们的初步研究表明，SCAP是负责根形成的早期茎祖细胞，这表明SCAP可能具有用于牙科组织再生的优势。在考虑任何临床应用中SCAP之前，重要的是要深入了解其干细胞特性。最近，我们发布了部分初步数据，以证明自体SCAP和PDLSC能够在新提取的牙齿的插座上产生根/牙周韧带组织，以作为在Minipigs中安装瓷冠的支持者。但是，这种早期的“原则证明”证据并不代表定期的临床植入程序。因此，我们建议探索使用SCAP和PDLSCS在厌食区域中再生根/牙周组织的潜力。这种方法可能会为未来潜在的临床应用提供关键的证据。 在此应用中，我们将表征人类和Minipig Scap的多元分化，然后利用Minipig Scap和PDLSC（能够形成牙周组织的干细胞种群）进行合作再生根/PDL复合物。为根/牙周组织再生选择小型曲子的原因是由于它们与人类的口面组织结构和牙科干细胞的特征相似。我们将使用分子，细胞，组织学，免疫学和干细胞移植方法来表征人类SCAP和Minipig SCAP/PDLSC。这项拟议的研究的最终目标是探索利用两个牙齿干细胞种群在临床前模型中重建生物学根/牙周复合物的潜力。我们预计我们在R21应用程序中提出的研究将来会导致R01应用。