title: Regenerative Endodontic Procedures: A Perspective from Stem Cell Niche Biology.
abstract: BACKGROUND
  Endodontics uses cell therapy strategies to treat pulpal and periapical diseases. During these therapies, surgeons aim to reconstruct the natural microenvironments that regulate the activity of dental stem cells.
  
  
  METHODS
  We searched for more than 400 articles in PubMed using key words from regenerative endodontics and dental stem cell biology. In 268 articles, we reviewed what factors may influence histologic results after preclinical dental treatments that use regenerative endodontic procedures after pulpectomy.
  
  
  RESULTS
  Several factors, such as the origin of stem cells, the biomimicry of scaffolds used, and the size of lesions, are considered to influence the histologic appearance of the regenerated pulp-dentin complex after treatments. Information is accumulating on transcription factors that generate the pulp-dentin complex and survival/trophic factors that would benefit niche recovery and histologic results.
  
  
  CONCLUSIONS
  In this article, we discuss the noninterchangeability of stem cells, the influence of dentin-entrapped molecule release on pulp regeneration and survival of stem cells, and the need of positional markers to assess treatments histologically. The ex vivo amplification of appropriate dental stem cells, the search for scaffolds storing the molecular diversity entrapped in the dentin, and the use of positional transcription factors as histologic markers are necessary to improve future preclinical experiments.
authors.affiliation: Department of Cell Biology, Genetics and Physiology, Faculty of Science, University of Málaga, Málaga, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), University of Málaga, Málaga, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Marí-Beffa
authors.affiliation: Department of Stomatology, Faculty of Dentistry, Joint CSIC-University of Seville Center, Seville, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Segura-Egea
authors.affiliation: Materials Science Institute of Seville (ICMS), Joint CSIC-University of Seville Center, Seville, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), University of Málaga, Málaga, Spain. Electronic address: aranzazu@icmse.csic.es.
authors.forename: Aránzazu
authors.initials: A
authors.lastname: Díaz-Cuenca
mesh_terms: D000818:Animals; D003782:Dental Pulp / Q000502:physiology; D003804:Dentin / Q000502:physiology; D006801:Humans; D012038:Regeneration; D044968:Regenerative Medicine / Q000379:methods*; D012390:Root Canal Therapy / Q000379:methods*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*
keywords: Biomaterial; endodontics; equivalence; regenerative endodontic procedures; stem cell niche; translational research