Xenogeneic bone filling materials modulate mesenchymal stem cell recruitment: role of the Complement C5a

  • Charlotte Jeanneau
  • Chloé Le Fournis
  • Imad AboutEmail author
Original Article



When bone filling materials are applied onto the periodontal tissues in vivo, they interact with the injured periodontal ligament (PDL) tissue and modulate its activity. This may lead to mesenchymal stem cells (MSCs) recruitment from bone marrow and initiate bone regeneration. Our hypothesis is that the filling materials affect PDL cells and MSCs functional activities by modulating PDL C5a secretion and subsequent MSCs proliferation and recruitment.

Materials and methods

Materials’ extracts were prepared from 3 bone-grafting materials: Gen-Os® of equine and porcine origins and bovine Bio-Oss®. Expression and secretion of C5a protein by injured PDL cells were investigated by RT-PCR and ELISA. MSCs proliferation was analyzed by MTT assay. C5a binding to MSCs C5aR and its phosphorylation was studied by ELISA. C5a implication in MSCs recruitment toward injured PDL cells was investigated using Boyden chambers.


MSCs proliferation significantly increased with Gen-Os® materials but significantly decreased with Bio-Oss®. C5a secretion slightly increased with Bio-Oss® while its level doubled with Gen-Os® materials. C5a fixation on MSCs C5aR and its phosphorylation significantly increased with Gen-Os® materials but not with Bio-Oss®. MSCs recruitment toward injured PDL cells increased with the three materials but was significantly higher with Gen-Os® materials than with Bio-Oss®. Adding C5a antagonist inhibited MSCs recruitment demonstrating a C5a-mediated migration.


Injured PDL cells secrete C5a leading MSCs proliferation and recruitment to the PDL injured cells. Gen-Os® materials enhanced both C5a secretion by injured PDL cells and MSCs recruitment. Bio-Oss® inhibited MSCs and was less efficient than Gen-Os® materials in inducing MSCs recruitment.

Clinical relevance

Within the limits of this study in vitro, Gen-Os® filling materials have a higher potential than Bio-Oss® on MSCs proliferation and C5a-dependent recruitment to the PDL injury site and the subsequent bone regeneration.


Xenogenic bone filling material Bone regeneration Complement C5a Stem cell recruitment 



The authors thank Dr. Jean-Charles GARDON for providing the teeth.

Funding information

The work was supported by Aix-Marseille University and CNRS.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Charlotte Jeanneau
    • 1
  • Chloé Le Fournis
    • 1
  • Imad About
    • 1
    Email author
  1. 1.Aix Marseille Univ, CNRS, ISM, Inst Movement SciMarseilleFrance

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