Tissue Engineering and Regenerative Medicine Laboratory (TERML), Columbia University Medical Center, New York, New York 10032, USA.
Tissue Eng Part A. 2010 Oct;16(10):3023-31. doi: 10.1089/ten.TEA.2010.0181.
Tooth infections or injuries involving dental pulp are treated routinely by root canal therapy. Endodontically treated teeth are devitalized, susceptible to re-infections, fractures, and subsequent tooth loss. Here, we report regeneration of dental-pulp-like tissue by cell homing and without cell transplantation. Upon in vivo implantation of endodontically treated real-size, native human teeth in mouse dorsum for the tested 3 weeks, delivery of basic fibroblast growth factor and/or vascular endothelial growth factor (bFGF and/or VEGF) yielded re-cellularized and revascularized connective tissue that integrated to native dentinal wall in root canals. Further, combined delivery of bFGF, VEGF, or platelet-derived growth factor (PDGF) with a basal set of nerve growth factor (NGF) and bone morphogenetic protein-7 (BMP7) generated cellularized and vascularized tissues positive of VEGF antibody staining and apparent neo-dentin formation over the surface of native dentinal wall in some, but not all, endodontically treated teeth. Newly formed dental pulp tissue appeared dense with disconnected cells surrounded by extracellular matrix. Erythrocyte-filled blood vessels were present with endothelial-like cell lining. Reconstructed, multiple microscopic images showed complete fill of dental-pulp-like tissue in the entire root canal from root apex to pulp chamber with tissue integration to dentinal wall upon delivery of bFGF, VEGF, or PDGF with a basal set of NGF and BMP7. Quantitative ELISA showed that combinatory delivery of bFGF, VEGF, or PDGF with basal NGF and BMP7 elaborated von Willerbrand factor, dentin sialoprotein, and NGF. These findings represent the first demonstration of regenerated dental-pulp-like tissue in endodontically treated root canals of real-size, native human teeth. The present chemotaxis-based approach has potent cell homing effects for re-cellularization and revascularization in endodontically treated root canals in vivo, although in an ectopic model. Regeneration of dental pulp by cell homing, rather than cell delivery, may accelerate clinical translation.
牙髓感染或损伤通常通过根管治疗来治疗。经过根管治疗的牙齿失去活力，容易再次感染、骨折和随后牙齿脱落。在这里，我们报告了通过细胞归巢而无需细胞移植来再生牙髓样组织。在体内将经过根管治疗的、大小与天然人牙相同的牙齿植入小鼠背部 3 周后，递送碱性成纤维细胞生长因子和/或血管内皮生长因子（bFGF 和/或 VEGF）可使再细胞化和再血管化的结缔组织与根管中的天然牙本质壁整合。此外，将 bFGF、VEGF 或血小板衍生生长因子（PDGF）与基本的神经生长因子（NGF）和骨形态发生蛋白 7（BMP7）一起递送，可在一些而非所有经过根管治疗的牙齿的天然牙本质壁表面上生成阳性 VEGF 抗体染色的细胞化和血管化组织，并出现明显的新牙本质形成。新形成的牙髓组织似乎很密集，细胞之间有细胞外基质。存在充满红细胞的血管，内皮样细胞衬里。重建的多个显微镜图像显示，在 bFGF、VEGF 或 PDGF 与基本 NGF 和 BMP7 一起递送时，从根尖到牙髓腔的整个根管中充满了牙髓样组织，并且组织与牙本质壁整合。定量 ELISA 显示，bFGF、VEGF 或 PDGF 与基本 NGF 和 BMP7 联合表达血管性血友病因子、牙本质涎磷蛋白和 NGF。这些发现代表了在大小与天然人牙相同的经过根管治疗的牙齿的根管中再生牙髓样组织的首次证明。目前基于趋化作用的方法具有在体内进行再细胞化和再血管化的强烈细胞归巢作用，尽管是在异位模型中。通过细胞归巢而不是细胞递送来再生牙髓可能会加速临床转化。
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