Kinetics of neo-vascularization during pulp regeneration

牙髓再生过程中新血管形成的动力学

• 批准号: 10378111
• 负责人: GEORGE T.J HUANG
• 金额: $ 19万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378111
• 关键词: Anastomosis - action; Animals; Blood Vessels; Cell physiology; Cells; Clinical; Clinical Protocols; Dental Pulp; Dentin; Deposition; Development; Endodontics; Endothelium; Engineering; Face; Human; In Vitro; Kinetics; Knowledge; Mediating; Modeling; Molecular; Natural regeneration; Outcome; Patients; Pericytes; Process; Property; Pulp Canals; Research Design; Root Canal Therapy; Skin; Study models; System; Technology; Testing; Time; Time Study; Tissues; Tooth structure; Tube; Vascular Endothelial Growth Factors; Vascular System; Vascular blood supply; Vascularization; angiogenesis; blood perfusion; cell type; clinical application; clinical practice; design; in vivo; mouse model; neovascular; neovascularization; neovasculature; new technology; novel strategies; stem cell based approach; stem cells; success

We have demonstrated that de novo pulp regeneration can be achieved via stem cell-based approaches. While such progress signifies the ultimate clinical practice of pulp regeneration on patients, one critical issue exists hindering the progress in this field: lack of timely vasculo/angiogenesis rendering inconsistent outcomes and narrowing the cases suitable for such practice (limited to immature teeth with wide open apex). Additionally, the kinetics of neo-vascularization during pulp regeneration is unknown. Without such knowledge, it is difficult to advance to the next level of pulp regeneration. Here, we propose to use combination of angiogenically induced dental pulp stem cells (DPSCs) and non- induced DPSCs to enhance the neo-vascularization during pulp regeneration. Most importantly, we designed a new study model that allows us to conduct real-time kinetic inspection of the cellular process during neo- vascularization under this approach. Overall hypothesis: Combination of angiogenically induced DPSCs and non-induced DPSCs allows accelerated and stabilized neo-vascularization thereby timely blood perfusion with the host vascular system can occur and more complete pulp regeneration can be reached. We will take the advantage of our newly designed tooth fragment skin-fold window chamber model, tube model, as well as our well-established tooth fragment model to test the hypothesis. Below are the Specific Aims. Aim 1. To Investigate the kinetics of the neo-vascularization of pulp regeneration using newly designed study models. • To use combination of angiogenically induced DPSCs that become endothelial-like cells (DPSC-ECs) and non-induced DPSCs for neo-vascularization. • To use tooth fragment skin-fold window chamber model to investigate the enhancement of vascularization and blood perfusion from the host vasculature to the engineered vasculature in real time. Aim 2. To investigate the neo-vascularization mechanism and long-term neo-vascular stability of regenerated pulp. • To examine molecular mechanisms of engineered vasculo/angiogenesis and anastomosis during pulp regeneration using tooth fragment skin-fold window chamber model. • To examine survival and long-term stability of engineered vasculature formed by DPSC-ECs plus DPSCs as well as the quality/quantity of the regenerated pulp in the tooth fragment model. The success of this project will allow this field to move closer to clinical applications, and potentially establishing a technology widely used in clinical endodontics.

我们已经证明可以通过基于干细胞的方法来实现从头纸浆再生。尽管 这样的进展表示果肉再生对患者的最终临床实践，存在一个关键问题 阻碍该领域的进展：缺乏及时的Vasculo/血管生成使结果不一致和 缩小适用于这种做法的案例（仅限于宽阔的顶点的未成熟牙齿）。另外， 纸浆再生过程中新血管化的动力学尚不清楚。没有这样的知识，很难 发展到新的纸浆再生水平。 在这里，我们建议使用血管生成诱导的牙髓干细胞（DPSC）和非 - 诱导的DPSC在纸浆再生过程中增强了新的血管化。最重要的是，我们设计了 新的研究模型，使我们能够对新的细胞过程进行实时动力学检查 这种方法下的血管化。 总体假设：血管生成诱导的DPSC和非诱导的DPSC的组合允许 加速和稳定的新血管形成，从而及时使用宿主血管系统的血液灌注可以 发生并可以达到更完整的纸浆再生。我们将利用我们新设计的 牙齿碎片皮肤折窗室模型，管模型以及我们公认的牙齿碎片 测试假设的模型。以下是具体目标。 目的1。使用新设计 研究模型。 •使用成为内皮样细胞（DPSC-EC）的血管生成诱导的DPSC的组合 和非诱导的DPSC用于新的血管化。 •使用牙齿碎片皮肤折窗室模型来研究增强 实时从宿主血管到工程脉管系统的血管化和血液灌注。 目的2。研究新的血管化机制和长期新血管稳定 再生纸浆。 •检查工程的Vasculo/血管生成的分子机制和纸浆过程中的吻合 使用牙齿碎片皮肤折窗室模型再生。 •检查由DPSC-ECS和DPSCS形成的工程脉管系统的生存和长期稳定性 以及牙齿碎片模型中再生纸浆的质量/数量。 该项目的成功将使该领域能够更接近临床应用程序，并有可能 建立一项广泛用于临床牙髓学的技术。