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实现牙髓从头再生。 这一进展标志着牙髓再生在患者身上的最终临床实践，但存在一个关键问题 阻碍该领域的进展：缺乏及时的血管/血管生成导致结果不一致和 缩小适合这种做法的病例范围（仅限于根尖张开的未成熟牙齿）。 如果没有这些知识，就很难了解牙髓再生过程中新血管形成的动力学。 推进纸浆再生的新水平。 在这里，我们建议结合使用血管生成诱导的牙髓干细胞（DPSC）和非 诱导 DPSC 增强牙髓再生过程中的新血管形成。 新的研究模型使我们能够对新生过程中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 DPSC 的组合允许 加速和稳定新生血管形成，及时血液灌注宿主血管系统，从而可以 发生并可以实现更完全的纸浆再生，我们将利用我们新设计的优势。 牙齿碎片皮褶窗室模型、管模型以及我们成熟的牙齿碎片 以下是具体目标。 目标 1. 使用新设计的材料研究牙髓再生的新血管形成动力学 研究模型。 • 使用血管生成诱导的 DPSC 组合，使其成为内皮样细胞 (DPSC-EC) 以及用于新血管形成的非诱导 DPSC。 • 使用牙齿碎片皮褶窗室模型来研究增强 从宿主脉管系统到工程化脉管系统的实时血管化和血液灌注。 目的2. 探讨新生血管形成机制及长期新生血管稳定性 再生纸浆。 • 检查牙髓过程中工程血管/血管生成和吻合的分子机制 使用牙齿碎片皮褶窗室模型进行再生。 • 检查由 DPSC-EC 和 DPSC 形成的工程脉管系统的存活率和长期稳定性 以及牙齿碎片模型中再生牙髓的质量/数量。 该项目的成功将使该领域更加接近临床应用，并有可能 建立广泛应用于临床牙髓病学的技术。