The Effects of Platelet-Derived Growth Factor-BB on Human Dental Pulp Stem Cells Mediated Dentin-Pulp Complex Regeneration

Abstract

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

In vitro and in vivo effects of concentrated growth factor on cells and tissues

“…Improvement of cell migration is the result of a high concentration of chemotactic factors, such as PDGF‐BB and bFGF in CGF. The effects of PDGF‐BB and bFGF on cell homing have been reported in previous studies (Takeuchi et al, ; Zhang et al, ). TGF and IGF‐I have also been shown to facilitate the migration of cells (Maucksch et al, ; Takai et al, ).…”

The potential application of concentrated growth factor in regenerative endodontics

“…Previous studies reported that over‐expressing PDGF‐BB in human dental pulp stem cells improved their proliferation and odontoblastic differentiation ability and also that PDGF‐BB can facilitate stem cell homing (Zhang et al . ). Takeuchi et al .…”

“…, Zhang et al . ). However, pulp regeneration is regulated by complex biological reactions associated with intricate signal molecules between cells and extracellular matrix.…”

Ageing affects the proliferation and mineralization of rat dental pulp stem cells under inflammatory conditions

“…, Zhang et al . ). In addition, DPSCs transplanted with granulocyte colony‐stimulating factor in collagen for dental pulp tissues regeneration after pulpectomy had excellent regeneration capacity (Nakashima et al .…”

“…Because of their excellent regenerative potential and repair ability, DPSCs have recently attracted substantial attention. DPSCs seeded on biocompatible scaffolds implanted subcutaneously in nude mice or in root canals of animal models have been reported to generate dentine-pulp complex structures (Chen et al 2015, Na et al 2016, Zhang et al 2017). In addition, DPSCs transplanted with granulocyte colony-stimulating factor in collagen for dental pulp tissues regeneration after pulpectomy had excellent regeneration capacity (Nakashima et al 2017).…”