Department of Prosthodontics, Shanghai, People's Republic of China.
Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, People's Republic of China.
Stem Cells Transl Med. 2017 Dec;6(12):2126-2134. doi: 10.1002/sctm.17-0033. Epub 2017 Oct 24.
Dentin-pulp complex regeneration is a promising alternative treatment for the irreversible pulpitis caused by tooth trauma or dental caries. This process mainly relies on the recruitment of endogenous or the transplanted dental pulp stem cells (DPSCs) to guide dentin-pulp tissue formation. Platelet-derived growth factor (PDGF), a well-known potent mitogenic, angiogenic, and chemoattractive agent, has been widely used in tissue regeneration. However, the mechanisms underlying the therapeutic effects of PDGF on dentin-pulp complex regeneration are still unclear. In this study, we tested the effect of PDGF-BB on dentin-pulp tissue regeneration by establishing PDGF-BB gene-modified human dental pulp stem cells (hDPSCs) using a lentivirus. Our results showed that PDGF-BB can significantly enhance hDPSC proliferation and odontoblastic differentiation. Furthermore, PDGF-BB and vascular endothelial growth factor (VEGF) secreted by hDPSCs enhanced angiogenesis. The chemoattractive effect of PDGF-BB on hDPSCs was also confirmed using a Transwell chemotactic migration model. We further determined that PDGF-BB facilitates hDPSCs migration via the activation of the phosphatidylinositol 3 kinase (PI3K)/Akt signaling pathway. In vivo, CM-DiI-labeled hDPSCs were injected subcutaneously into mice, and our results showed that more labeled cells were recruited to the sites implanted with calcium phosphate cement scaffolds containing PDGF-BB gene-modified hDPSCs. Finally, the tissue-engineered complexes were implanted subcutaneously in mice for 12 weeks, the Lenti-PDGF group generated more dentin-like mineralized tissue which showed positive staining for the DSPP protein, similar to tooth dentin tissue, and was surrounded by highly vascularized dental pulp-like connective tissue. Taken together, our data demonstrated that the PDGF-BB possesses a powerful function in prompting stem cell-based dentin-pulp tissue regeneration. Stem Cells Translational Medicine 2017;6:2126-2134.
牙髓-牙本质复合体再生是一种有前途的替代治疗方法，可用于治疗由牙外伤或龋齿引起的不可复性牙髓炎。这个过程主要依赖于内源性或移植的牙髓干细胞（DPSCs）募集来指导牙本质-牙髓组织的形成。血小板衍生生长因子（PDGF）是一种众所周知的有效的有丝分裂原、血管生成和趋化因子，已被广泛应用于组织再生。然而，PDGF 对牙髓-牙本质复合体再生的治疗效果的机制仍不清楚。在这项研究中，我们通过使用慢病毒建立 PDGF-BB 基因修饰的人牙髓干细胞（hDPSCs）来测试 PDGF-BB 对牙本质-牙髓组织再生的影响。我们的结果表明，PDGF-BB 可显著增强 hDPSC 的增殖和成牙本质分化。此外，hDPSCs 分泌的 PDGF-BB 和血管内皮生长因子（VEGF）增强了血管生成。使用 Transwell 趋化迁移模型也证实了 PDGF-BB 对 hDPSCs 的趋化作用。我们进一步确定，PDGF-BB 通过激活磷脂酰肌醇 3 激酶（PI3K）/Akt 信号通路促进 hDPSCs 的迁移。在体内，CM-DiI 标记的 hDPSCs 被皮下注射到小鼠体内，我们的结果表明，更多的标记细胞被募集到植入含有 PDGF-BB 基因修饰的 hDPSCs 的磷酸钙水泥支架的部位。最后，组织工程复合物被皮下植入小鼠体内 12 周，Lenti-PDGF 组产生了更多的牙本质样矿化组织，DSPP 蛋白染色阳性，类似于牙本质组织，并被富含血管的牙髓样结缔组织包围。综上所述，我们的数据表明，PDGF-BB 在促进基于干细胞的牙髓-牙本质组织再生方面具有强大的功能。
