title: Dental Pulp Tissue Regeneration Using Dental Pulp Stem Cells Isolated and Expanded in Human Serum.
abstract: BACKGROUND
  Dental pulp-derived stem cells (DPSCs) have the potential to regenerate dentin and dental pulp tissue because of their differentiation capacity and angiogenic properties. However, for regenerative approaches to gain regulatory and clinical acceptance, protocols are needed to determine more feasible ways to cultivate DPSCs, namely, without the use of xenogeneic-derived components (animal sera) and exogenous growth factors.
  
  
  METHODS
  In this study, human DPSCs were isolated from third molars and expanded in standard culture conditions containing fetal bovine serum (DPSCs-FBS) or conditions containing human serum (DPSCs-HS). After cell characterization and evaluation of their angiogenic secretome, DPSCs were seeded in tooth slice/scaffolds and implanted subcutaneously into immunodeficient mice. After 30 days, tooth slices were retrieved and evaluated for dental pulp tissue regeneration. Immunohistochemistry and confocal microscopy were used to quantify blood vessel formation and evaluate predentin and dentin formation.
  
  
  RESULTS
  After culture, DPSCs-HS produced concentrations of angiogenic growth factors equivalent to DPSCs-FBS. Additionally, in DPSCs-HS, several angiogenic factors were produced in at least 1-fold higher concentrations than in DPSCs-FBS. In vivo, it was determined that DPSCs-HS produced a robust angiogenic response and regeneration of dentin equivalent to DPSCs-FBS.
  
  
  CONCLUSIONS
  These findings show that DPSCs can be isolated and expanded to clinical scale numbers in media devoid of animal serum or exogenous growth factors and still maintain their pulp regenerative properties. The implications of these findings are significant for further development of clinical protocols using DPSCs in cell therapies.
authors.affiliation: Department of Cariology and Restorative Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Evandro
authors.initials: E
authors.lastname: Piva
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Tarlé
authors.affiliation: Department of Cariology and Restorative Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Nör
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Duohong
authors.initials: D
authors.lastname: Zou
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hatfield
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Tyler
authors.initials: T
authors.lastname: Guinn
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Eubanks
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan. Electronic address: dkaigler@umich.edu.
authors.forename: Darnell
authors.initials: D
authors.lastname: Kaigler
mesh_terms: D000293:Adolescent; D049109:Cell Proliferation; D003470:Culture Media; D003782:Dental Pulp / Q000166:cytology / Q000502:physiology*; D006801:Humans; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D054457:Tissue Scaffolds; D055815:Young Adult
chemical_list: D003470:Culture Media
keywords: Angiogenesis; cell therapy; dental pulp stem cells; dentin; pulp tissue engineering