Bone tissue formation with human mesenchymal stem cells and biphasic calcium phosphate ceramics: the local implication of osteoclasts and macrophages

Biomaterials. 2014 Dec;35(36):9660-7. doi: 10.1016/j.biomaterials.2014.08.018. Epub 2014 Aug 29.


Human mesenchymal stem cells (hMSC) have immunomodulative properties and, associated with calcium phosphate (CaP) ceramics, induce bone tissue repair. However, the mechanisms of osteoinduction by hMSC with CaP are not clearly established, in particular the role of osteoclasts and macrophages. Biphasic calcium phosphate (BCP) particles were implanted with or without hMSC in the paratibial muscles of nude mice. hMSC increased osteoblastic gene expression at 1 week, the presence of macrophages at 2 and 4 weeks, osteoclastogenesis at 4 and 8 weeks, and osteogenesis at 4 and 8 weeks. hMSC disappeared from the implantation site after 2 weeks, indicating that hMSC were inducers rather than effectors of bone formation. Induced blockage of osteoclastogenesis by anti-Rankl treatment significantly impaired bone formation, revealing the pivotal role of osteoclasts in bone formation. In summary, hMSC positively influence the body foreign reaction by attracting circulating haematopoietic stem cells and inducing their differentiation into macrophages M1 and osteoclasts, thus favouring bone formation.

Keywords: Foreign body reaction; Macrophages; Osteoclasts; Osteoinduction; mAb anti-RANKL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Ceramics / pharmacology*
  • Foreign Bodies / etiology
  • Humans
  • Hydroxyapatites / administration & dosage
  • Hydroxyapatites / pharmacology*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • Mice, Nude
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects
  • Osteogenesis / drug effects*
  • Prostheses and Implants / adverse effects
  • RANK Ligand / antagonists & inhibitors


  • Antibodies, Monoclonal
  • Hydroxyapatites
  • RANK Ligand
  • hydroxyapatite-beta tricalcium phosphate