Fibroblast growth factor 2 and platelet-derived growth factor, but not platelet lysate, induce proliferation-dependent, functional class II major histocompatibility complex antigen in human mesenchymal stem cells

Chiara Bocelli-Tyndall, Paul Zajac, Nunzia Di Maggio, Emanuele Trella, Federica Benvenuto, Giandomenica Iezzi, Arnaud Scherberich, Andrea Barbero, Stefan Schaeren, Vito Pistoia, Giulio Spagnoli, Mirko Vukcevic, Ivan Martin, Alan Tyndall

Research output: Contribution to journalArticle

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Abstract

Objective. To document the specificity and the mechanism of induction of a novel class II major histocompatibility complex (MHC) antigen by mitogenic growth factors in human mesenchymal stem cells (MSCs) expanded in vitro for translational applications. Methods. Expression of class II MHC molecules was measured in human MSCs and differentiated cells expanded in the presence of fibroblast growth factor 2 (FGF-2), platelet-derived growth factor BB (PDGF-BB), human platelet lysate, or interferon-γ (IFNγ). The roles of cell proliferation and growth factor-induced signaling pathways were investigated as well as the class II MHC assembly machinery and functional capacity. Results. FGF-2 and, to a lesser extent, PDGF-BB induced in adult human MSCs the expression of HLA-DR (normally induced by inflammatory cytokines), which was able to stimulate CD4+ T cells via superantigen binding. In contrast to IFNγ, FGF induced HLA-DR expression only in human MSCs proliferating under its mitogenic effect and not in mouse MSCs or in differentiated human cells. Although it induced cell proliferation, human platelet lysate did not cause HLA-DR expression in human MSCs. HLA-DR expression occurred following FGF-specific binding to its receptor(s), mainly FGF receptor 1, without inducing IFNγ or tumor necrosis factor α expression. Both MAPK/ERK-1/2 and phosphatidylinositol 3-kinase/Akt controlled cell proliferation and HLA-DR expression, but only MAPK/ERK-1/2 controlled the induction of the class II MHC transcription activator protein CIITA, the major determinant of HLA-DR transcription. Conclusion. The induction of functional HLA-DR in proliferating progenitor MSCs is a property of human MSCs that have been expanded with mitogenic growth factors. This has potential biologic significance in the regulation and/or protection of progenitor cell subpopulations under sustained mitogenic proliferation and needs to be taken into account when expanding MSCs for use in in vivo applications.

Original languageEnglish
Pages (from-to)3815-3825
Number of pages11
JournalArthritis and Rheumatism
Volume62
Issue number12
DOIs
Publication statusPublished - Dec 2010

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Platelet-Derived Growth Factor
Histocompatibility Antigens Class II
Fibroblast Growth Factor 2
Major Histocompatibility Complex
Mesenchymal Stromal Cells
HLA-DR Antigens
Blood Platelets
Interferons
Intercellular Signaling Peptides and Proteins
Cell Proliferation
Phosphatidylinositol 3-Kinase
Fibroblast Growth Factor 1
Fibroblast Growth Factor Receptors
Superantigens
Stem Cells
Tumor Necrosis Factor-alpha
Cytokines
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Fibroblast growth factor 2 and platelet-derived growth factor, but not platelet lysate, induce proliferation-dependent, functional class II major histocompatibility complex antigen in human mesenchymal stem cells. / Bocelli-Tyndall, Chiara; Zajac, Paul; Di Maggio, Nunzia; Trella, Emanuele; Benvenuto, Federica; Iezzi, Giandomenica; Scherberich, Arnaud; Barbero, Andrea; Schaeren, Stefan; Pistoia, Vito; Spagnoli, Giulio; Vukcevic, Mirko; Martin, Ivan; Tyndall, Alan.

In: Arthritis and Rheumatism, Vol. 62, No. 12, 12.2010, p. 3815-3825.

Research output: Contribution to journalArticle

Bocelli-Tyndall, C, Zajac, P, Di Maggio, N, Trella, E, Benvenuto, F, Iezzi, G, Scherberich, A, Barbero, A, Schaeren, S, Pistoia, V, Spagnoli, G, Vukcevic, M, Martin, I & Tyndall, A 2010, 'Fibroblast growth factor 2 and platelet-derived growth factor, but not platelet lysate, induce proliferation-dependent, functional class II major histocompatibility complex antigen in human mesenchymal stem cells', Arthritis and Rheumatism, vol. 62, no. 12, pp. 3815-3825. https://doi.org/10.1002/art.27736
Bocelli-Tyndall, Chiara ; Zajac, Paul ; Di Maggio, Nunzia ; Trella, Emanuele ; Benvenuto, Federica ; Iezzi, Giandomenica ; Scherberich, Arnaud ; Barbero, Andrea ; Schaeren, Stefan ; Pistoia, Vito ; Spagnoli, Giulio ; Vukcevic, Mirko ; Martin, Ivan ; Tyndall, Alan. / Fibroblast growth factor 2 and platelet-derived growth factor, but not platelet lysate, induce proliferation-dependent, functional class II major histocompatibility complex antigen in human mesenchymal stem cells. In: Arthritis and Rheumatism. 2010 ; Vol. 62, No. 12. pp. 3815-3825.
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abstract = "Objective. To document the specificity and the mechanism of induction of a novel class II major histocompatibility complex (MHC) antigen by mitogenic growth factors in human mesenchymal stem cells (MSCs) expanded in vitro for translational applications. Methods. Expression of class II MHC molecules was measured in human MSCs and differentiated cells expanded in the presence of fibroblast growth factor 2 (FGF-2), platelet-derived growth factor BB (PDGF-BB), human platelet lysate, or interferon-γ (IFNγ). The roles of cell proliferation and growth factor-induced signaling pathways were investigated as well as the class II MHC assembly machinery and functional capacity. Results. FGF-2 and, to a lesser extent, PDGF-BB induced in adult human MSCs the expression of HLA-DR (normally induced by inflammatory cytokines), which was able to stimulate CD4+ T cells via superantigen binding. In contrast to IFNγ, FGF induced HLA-DR expression only in human MSCs proliferating under its mitogenic effect and not in mouse MSCs or in differentiated human cells. Although it induced cell proliferation, human platelet lysate did not cause HLA-DR expression in human MSCs. HLA-DR expression occurred following FGF-specific binding to its receptor(s), mainly FGF receptor 1, without inducing IFNγ or tumor necrosis factor α expression. Both MAPK/ERK-1/2 and phosphatidylinositol 3-kinase/Akt controlled cell proliferation and HLA-DR expression, but only MAPK/ERK-1/2 controlled the induction of the class II MHC transcription activator protein CIITA, the major determinant of HLA-DR transcription. Conclusion. The induction of functional HLA-DR in proliferating progenitor MSCs is a property of human MSCs that have been expanded with mitogenic growth factors. This has potential biologic significance in the regulation and/or protection of progenitor cell subpopulations under sustained mitogenic proliferation and needs to be taken into account when expanding MSCs for use in in vivo applications.",
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AU - Zajac, Paul

AU - Di Maggio, Nunzia

AU - Trella, Emanuele

AU - Benvenuto, Federica

AU - Iezzi, Giandomenica

AU - Scherberich, Arnaud

AU - Barbero, Andrea

AU - Schaeren, Stefan

AU - Pistoia, Vito

AU - Spagnoli, Giulio

AU - Vukcevic, Mirko

AU - Martin, Ivan

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