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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 and Zajac, Paul and Di Maggio, Nunzia and Trella, Emanuele and Benvenuto, Federica and Iezzi, Giandomenica and Scherberich, Arnaud and Barbero, Andrea and Schaeren, Stefan and Pistoia, Vito and Spagnoli, Giulio and Vukcevic, Mirko and Martin, Ivan and Tyndall, Alan. (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 & Rheumatism, 62 (12). pp. 3815-3825.

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Official URL: http://edoc.unibas.ch/dok/A6006671

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Rheumatologie FPS (Tyndall)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Rheumatologie FPS (Tyndall)
03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Rheumatologie FPS (Tyndall)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Bewegungsapparat und Integument > Traumatologie (Jakob)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Bewegungsapparat und Integument > Traumatologie (Jakob)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cell and Gene Therapy (Banfi/Heberer)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Oncology Surgery (Spagnoli/Heberer)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Tissue Engineering (Martin/Heberer)
UniBasel Contributors:Martin, Ivan and Zajac, Paul and Schären, Stefan and Barbero, Andrea and Spagnoli, Giulio C. and De Vere-Tyndall, Alan and Scherberich, Arnaud
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Wiley
ISSN:0004-3591
e-ISSN:1529-0131
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Oct 2017 09:13
Deposited On:21 Jun 2013 12:25

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