title: Effects of a ceramic biomaterial on immune modulatory properties and differentiation potential of human mesenchymal stromal cells of different origin.
abstract: 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.
authors.affiliation: 1 Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona , Verona, Italy .
authors.forename: Giulio
authors.initials: G
authors.lastname: Bassi
authors.forename: Fabien
authors.initials: F
authors.lastname: Guilloton
authors.forename: Cedric
authors.initials: C
authors.lastname: Menard
authors.forename: Mariano
authors.initials: M
authors.lastname: Di Trapani
authors.forename: Frederic
authors.initials: F
authors.lastname: Deschaseaux
authors.forename: Luc
authors.initials: L
authors.lastname: Sensebé
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.forename: Rosaria
authors.initials: R
authors.lastname: Giordano
authors.forename: Philippe
authors.initials: P
authors.lastname: Bourin
authors.forename: Massimo
authors.initials: M
authors.lastname: Dominici
authors.forename: Karin
authors.initials: K
authors.lastname: Tarte
authors.forename: Mauro
authors.initials: M
authors.lastname: Krampera
mesh_terms: D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002516:Ceramics / Q000737:chemistry / Q000494:pharmacology; D017886:Durapatite / Q000737:chemistry / Q000494:pharmacology*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology; D056747:Immunomodulation / Q000187:drug effects / Q000276:immunology*; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology*; D054457:Tissue Scaffolds
chemical_list: D018786:Bone Substitutes; D002130:Calcium Phosphates; D007155:Immunologic Factors; D017886:Durapatite; C485829:calcium phosphate, dibasic, anhydrous