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PDGF-modified human Dental Pulp Stem Cells: The End of Toothache as we know it?

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Review of “The Effects of Platelet-Derived Growth Factor-BB on Human Dental Pulp Stem Cells Mediated Dentin-Pulp Complex Regeneration” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Tooth trauma or dental caries can lead to the inflammation of dental pulp tissue, the all too familiar pain of toothache, and potentially irreversible damage. Researchers from the laboratories of Xinquan Jiang and Wenjie Zhang (Shanghai Jiao Tong University, PR China) hoped to promote dental tissue regeneration via the application of stem cells resident within the human dental pulp (hDPSCs) [1, 2]. However, previous studies had indicated that hDPSCs exhibited insufficient mineral-forming capabilities to permit adequate tooth repair [3, 4]. 

In a new STEM CELLS Translational Medicine study, Zhang et al. now report that the overexpression of Platelet-Derived Growth Factor-BB (PDGF-BB), a well-known potent mitogenic, angiogenic, and chemoattractive agent, can significantly enhance dental tissue regeneration [5]. Have this team of researchers discovered the end to toothache as we know it?

The authors first stably transduced freshly derived multipotent early passage hDPSCs with a PDGF-BB expression vector, generating cells that displayed heightened proliferation when compared to control hDPSCs. Additionally, modified hDPSCs expressed elevated levels of odontogenic marker genes involved in tooth development and dentin mineralization, indicating odontoblastic differentiation, and attached and spread well on the surface of calcium phosphate cement (CPC) scaffolds employed for implantation. 

Interestingly, PDGF-BB overexpression by modified hDPSCs enhanced the recruitment of hDPSCs both in vitro and in vivo via the activation of the phosphatidylinositol 3 kinase (PI3K)/Akt signaling pathway and, in combination with secreted vascular endothelial growth factor (VEGF), enhanced in vitro angiogenesis. Furthermore, when the authors assessed the subcutaneous implantation of hDPSCs grown on CPD scaffolds, they discovered that PDGF-BB modified cells generated more dentin-like mineralized tissue surrounded by highly vascularized dental pulp-like connective tissue at 12 weeks when compared to unmodified hDPSCs.

Could the new approach represent the end of toothache as we know it? To find out, stay tuned to the Stem Cells Portal for more original and innovative studies on stem cell-mediated dental tissue regeneration!

Further Reading

Press Release: Study shows how growth factor aids stem cells’ ability to regenerate damaged teeth

Discussion Points

  • Can modified hDPSCs be maintained and expanded in in vitro culture over long periods of time?
  • Are modified hDPSCs safe in the long-term?
  • Can other factors help to improve hDPSC-mediated tooth repair

References

  1. Mao, Jeremy J. and Darwin J. Prockop, Stem Cells in the Face: Tooth Regeneration and Beyond. Cell Stem Cell 2012;11:291-301.
  2. Gronthos, S., et al., Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proceedings of the National Academy of Sciences 2000;97:13625-13630.
  3. Zhang, W., et al., The performance of human dental pulp stem cells on different three-dimensional scaffold materials. Biomaterials 2006;27:5658-5668.
  4. Zhang, W., et al., Hard Tissue Formation in a Porous HA/TCP Ceramic Scaffold Loaded with Stromal Cells Derived from Dental Pulp and Bone Marrow. Tissue Engineering Part A 2008;14:285-294.
  5. Zhang, M., et al., The Effects of Platelet-Derived Growth Factor-BB on Human Dental Pulp Stem Cells Mediated Dentin-Pulp Complex Regeneration. STEM CELLS Translational Medicine 2017;6:2126-2134.