Effects of a ceramic biomaterial on immune modulatory properties and differentiation potential of human mesenchymal stromal cells of different origin

Tissue Eng Part A. 2015 Feb;21(3-4):767-81. doi: 10.1089/ten.TEA.2014.0269. Epub 2014 Dec 11.


The aim of this study was to assess the immune modulatory properties of human mesenchymal stromal cells obtained from bone marrow (BM-MSCs), fat (ASCs), and cord blood (CB-MSCs) in the presence of a hydroxyapatite and tricalcium-phosphate (HA/TCP) biomaterial as a scaffold for MSC delivery. In resting conditions, a short-term culture with HA/TCP did not modulate the anti-apoptotic and suppressive features of the various MSC types toward T, B, and NK cells; in addition, when primed with inflammatory cytokines, MSCs similarly increased their suppressive capacities in the presence or absence of HA/TCP. The long-term culture of BM-MSCs with HA/TCP induced an osteoblast-like phenotype with upregulation of OSTERIX and OSTEOCALCIN, similar to what was obtained with dexamethasone and, to a higher extent, with bone morphogenetic protein 4 (BMP-4) treatment. MSC-derived osteoblasts did not trigger immune cell activation, but were less efficient than undifferentiated MSCs in inhibiting stimulated T and NK cells. Interestingly, their suppressive machinery included not only the activation of indoleamine-2,3 dioxygenase (IDO), which plays a central role in T-cell inhibition, but also cyclooxygenase-2 (COX-2) that was not significantly involved in the immune modulatory effect of human undifferentiated MSCs. Since COX-2 is significantly involved in bone healing, its induction by HA/TCP could also contribute to the therapeutic activity of MSCs for bone tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Substitutes / chemistry
  • Bone Substitutes / pharmacology
  • Calcium Phosphates / chemistry
  • Calcium Phosphates / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Ceramics / chemistry
  • Ceramics / pharmacology
  • Durapatite / chemistry
  • Durapatite / pharmacology*
  • Equipment Design
  • Equipment Failure Analysis
  • Humans
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology
  • Immunomodulation / drug effects
  • Immunomodulation / immunology*
  • Materials Testing
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / immunology*
  • Tissue Scaffolds*


  • Bone Substitutes
  • Calcium Phosphates
  • Immunologic Factors
  • Durapatite
  • calcium phosphate, dibasic, anhydrous