The influence of hypoxia on the differentiation capacities and immunosuppressive properties of clonal mouse mesenchymal stromal cell lines.
Multipotent mesenchymal stromal cells are multipotent cells capable of differentiating into different mesodermal cell types. Enigmatically, mesenchymal stromal cells present in the bone marrow support early lymphopoiesis yet can inhibit mature lymphocyte growth. Critical features of the bone marrow microenvironment, such as the level of oxygen, play an important role in mesenchymal stromal cell biology. Herein, we show that a panel of continuously growing mouse mesenchymal stromal cell lines, namely OP9, MS5, PA6, ST2 and B16-14, exhibit mesenchymal stromal cell characteristic phenotypes and respond physiologically to oxygen deprivation. Culturing freshly isolated bone marrow-derived mesenchymal stromal cells or cell lines at 5% O2 resulted in a dramatic increase in expression of hypoxia-inducible factor family members and of key genes involved in their differentiation. Phenotypically, their osteogenic and adipogenic differentiation capacity was generally improved in hypoxia, whereas their inhibitory effects on in vitro T-cell proliferation were preserved. Taken together, we conclude that these continuously growing mouse cell lines behave as canonical mesenchymal stromal cells and respond physiologically to hypoxia, thereby providing a potent tool for the study of different aspects of mesenchymal stromal cell biology.
Regenerative Medicine Institute, National Centre for Biomedical Engineering Science and School of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland.
Sonia
S
Prado-Lòpez
Regenerative Medicine Institute, National Centre for Biomedical Engineering Science and School of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland.
Michelle M
MM
Duffy
Regenerative Medicine Institute, National Centre for Biomedical Engineering Science and School of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland.
Claas
C
Baustian
Regenerative Medicine Institute, National Centre for Biomedical Engineering Science and School of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland.
Senthilkumar
S
Alagesan
Regenerative Medicine Institute, National Centre for Biomedical Engineering Science and School of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland.
Shirley A
SA
Hanley
Regenerative Medicine Institute, National Centre for Biomedical Engineering Science and School of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland.
Alessia
A
Stocca
Regenerative Medicine Institute, National Centre for Biomedical Engineering Science and School of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland.
Matthew D
MD
Griffin
Regenerative Medicine Institute, National Centre for Biomedical Engineering Science and School of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland.
Rhodri
R
Ceredig
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002460:Cell Line; D020219:Chondrogenesis / Q000235:genetics; D020869:Gene Expression Profiling; D056747:Immunomodulation; D016130:Immunophenotyping; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D010641:Phenotype
D015415:Biomarkers