期刊
TISSUE ENGINEERING PART A
卷 21, 期 3-4, 页码 767-781出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2014.0269
关键词
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资金
- seventh Framework Program of the European Commission: CASCADE [FP7-HEALTH-233236]
- seventh Framework Program of the European Commission: REBORNE Regenerating bone defects using new biomedical approaches [FP7-HEALTH-241879]
- Italian Ministry of University and Scientific Research-PRIN
- Ricerca Sanitaria Finalizzata
- Cariverona Foundation, Verona, Italy (Bando)
- European Center for Transplantation Sciences and Immunotherapy (IHU CESTI) [ANR-10-IBHU-0005]
- Infrastructure Program ECELL-FRANCE [ANR-11-INSB-005]
- CPER
- Agence Nationale de la Recherche (ANR) [ANR-10-IBHU-0005] Funding Source: Agence Nationale de la Recherche (ANR)
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.
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