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）：本申请的目的是进一步表征新鉴定的源自根尖乳头（SCAP）的干细胞，并探索使用SCAP与牙周膜干细胞（PDLSC）通过常规临床牙种植手术在小型猪模型中再生无牙区域牙根/牙周组织的潜力。我们最近分离出了人类 SCAP，并发现其与其他牙髓干细胞（如牙髓干细胞 (DPSC)）的独特特性。特别是，SCAP 显示出体内牙本质再生能力的增加、独特的基因表达谱以及可检测水平的端粒酶活性。我们的初步研究表明，SCAP 是负责牙根形成的早期干祖细胞，这表明 SCAP 可能具有用于牙组织再生的优势。在考虑 SCAP 进行任何临床应用之前，深入了解其干细胞特性至关重要。最近，我们发表了部分初步数据，证明自体SCAP和PDLSC能够在新拔牙的牙槽窝中生成根/牙周膜组织，作为小型猪安装烤瓷冠的支撑体。然而，这种早期的“原理证明”证据并不代表常规的临床植入程序。因此，我们建议探索使用 SCAP 和 PDLSC 在无牙颌区域再生牙根/牙周组织的潜力，模仿临床牙种植治疗。该方法可能为未来潜在的临床应用提供关键证据。 在此应用中，我们将表征人类和小型猪 SCAP 的多能分化，然后利用小型猪 SCAP 和 PDLSC（一种能够形成牙周组织的干细胞群）来协同再生根/PDL 复合物。之所以选择小型猪进行根/牙周组织再生，是因为它们的口面部组织结构和牙干细胞特征与人类相似。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 和小型猪 SCAP/PDLSC。这项研究的最终目标是探索利用两种牙干细胞群在临床前模型中重建生物牙根/牙周复合体的潜力。我们预计我们在此 R21 应用中提出的研究将在未来产生 R01 应用。