Postnatal Stem Cell-Mediated Tooth Regeneration

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顶乳头（SCAP）的干细胞，并探索使用SCAP沿着牙周韧带干细胞（PDLSC）再生无牙区根/牙周组织的潜力。通过小型猪模型中的定期临床牙科植入手术。我们最近分离了人SCAP，并发现其与其他牙齿干细胞如牙髓干细胞（DPSC）不同的特性。特别是，SCAP显示出体内牙本质再生能力增加，独特的基因表达谱和可检测的端粒酶活性水平。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。在考虑将SCAP用于任何临床应用之前，深入了解其干细胞特性至关重要。最近，我们发表了我们的部分初步数据，证明自体SCAP和PDLSCs能够在新拔出的牙齿的窝中产生根/牙周膜组织，作为小型猪安装烤瓷冠的支持物。然而，这种早期的“原理证明”证据并不代表常规的临床植入手术。因此，我们建议探索使用SCAP和PDLSCs在无牙区模拟临床牙科种植治疗的牙根/牙周组织再生的潜力。这种方法可能为未来的潜在临床应用提供关键证据。 在本申请中，我们将表征人和小型猪SCAP的多能分化，然后利用小型猪SCAP和PDLSC，能够形成牙周组织的干细胞群，合作再生根/PDL复合物。选择小型猪进行根/牙周组织再生的原因是由于它们在口面组织结构和牙齿干细胞特性方面与人类相似。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SCAP和小型猪SCAP/PDLSC。本研究的最终目的是探索利用两种牙源性干细胞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R21应用中提出的研究将在未来导致R 01应用。

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.