title: Complement C3a Mobilizes Dental Pulp Stem Cells and Specifically Guides Pulp Fibroblast Recruitment.
abstract: BACKGROUND
  Complement activation is considered a major mechanism in innate immunity. Although it is mainly involved in initiating inflammation, recent data reported its involvement in other processes such as tissue regeneration. In the dental pulp, complement C5a fragment has been shown to be involved in the recruitment of dental pulp stem cells (DPSCs). This study sought to investigate the possible role of C3a, another complement fragment, in the early steps of dentin-pulp regeneration.
  
  
  METHODS
  Expression of C3a receptor (C3aR) was investigated by immunofluorescence and reverse transcriptase polymerase chain reaction on cultured pulp fibroblasts, STRO-1-sorted DPSCs, as well as on human tooth sections in vivo. The effect of C3a on proliferation of both DPSCs and pulp fibroblasts was investigated by MTT assay. Cell migration under a C3a gradient was investigated by using microfluidic chemotaxis chambers.
  
  
  RESULTS
  C3aR was expressed in vivo as well as in cultured pulp fibroblasts co-expressing fibroblast surface protein and in DPSCs co-expressing STRO-1. Addition of recombinant C3a induced a significant proliferation of both cell types. When subjected to a C3a gradient, DPSCs were mobilized but not specifically recruited, whereas pulp fibroblasts were specifically recruited following a C3a gradient.
  
  
  CONCLUSIONS
  These results provide the first demonstration of C3aR expression in the dental pulp and demonstrate that C3a is involved in increasing DPSCs and fibroblast proliferation, in mobilizing DPSCs, and in specifically guiding fibroblast recruitment. This provides an additional link to the tight correlation between inflammation and tissue regeneration.
authors: Aix Marseille Université, CNRS, ISM, Institute of Movement Sciences, Marseille, France.
authors: Pierre
authors: P
authors: Rufas
authors: Aix Marseille Université, CNRS, ISM, Institute of Movement Sciences, Marseille, France.
authors: Charlotte
authors: C
authors: Jeanneau
authors: Aix Marseille Université, CNRS, ISM, Institute of Movement Sciences, Marseille, France.
authors: Charlotte
authors: C
authors: Rombouts
authors: Aix Marseille Université, CNRS, ISM, Institute of Movement Sciences, Marseille, France; APHM, Service d'Odontologie, Hôpital Timone, Marseille, France.
authors: Patrick
authors: P
authors: Laurent
authors: Aix Marseille Université, CNRS, ISM, Institute of Movement Sciences, Marseille, France. Electronic address: imad.about@univ-amu.fr.
authors: Imad
authors: I
authors: About
mesh_terms: D000954:Antigens, Surface / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D015926:Complement C3a / Q000502:physiology*; D003782:Dental Pulp / Q000166:cytology* / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology*
chemical_list: D000954:Antigens, Surface; C525591:STRO-1 antigen, human; D015926:Complement C3a
keywords: Chemotaxis; complement; dentin-pulp; microfluidics; regeneration