Differentiation of mesenchymal stem cells under hypoxia and normoxia: lipid profiles revealed by time-of-flight secondary ion mass spectrometry and multivariate analysis.
Mesenchymal stem cells (MSC) have the ability to self-renew and differentiate into multiple cell types valuable for clinical treatment of rheumatic pathologies. To study the chondrogenic potential of MSC and identify the conditions that recreate the native cartilage environment, we used time-of-flight secondary ion mass spectrometry (TOF-SIMS) for label-free detection of cell-type- and environmental-condition-specific molecular profiles. We observed that coculture of human MSC and chondrocytes under standard culture conditions leads to improved extracellular matrix (ECM) deposition. In marked contrast, this effect was lost under low oxygen tension. This improved extracellular matrix deposition was associated with a significant decrease in lipids and in particular cholesterol under low oxygen tension as revealed by TOF-SIMS coupled to principal component analysis and discriminant analysis. We furthermore demonstrate that the higher cholesterol levels under normoxia might regulate fibroblast growth factor 1 (FGF-1) gene expression which was previously implemented in increased ECM production in the cocultures. In conclusion, our study shows an unexpected role of lipids as orchestrators of chondrogenesis in response to oxygen tension which is, at least in part, mediated through FGF-1.
†Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, 7522 NB Enschede, The Netherlands.
Nicole
N
Georgi
‡Biomolecular Imaging Mass Spectrometry, FOM Institute AMOLF, 1098 XG Amsterdam, The Netherlands.|§The Maastricht Multimodal Molecular Imaging Institute, M4I, Maastricht University, 6229 ER Maastricht, The Netherlands.
Berta
B
Cillero-Pastor
‡Biomolecular Imaging Mass Spectrometry, FOM Institute AMOLF, 1098 XG Amsterdam, The Netherlands.
Gert B
GB
Eijkel
†Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, 7522 NB Enschede, The Netherlands.
Parthiban C
PC
Periyasamy
‡Biomolecular Imaging Mass Spectrometry, FOM Institute AMOLF, 1098 XG Amsterdam, The Netherlands.
Andras
A
Kiss
∥Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, 7522 NB Enschede, The Netherlands.
Clemens
C
van Blitterswijk
†Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, 7522 NB Enschede, The Netherlands.
Janine N
JN
Post
‡Biomolecular Imaging Mass Spectrometry, FOM Institute AMOLF, 1098 XG Amsterdam, The Netherlands.|§The Maastricht Multimodal Molecular Imaging Institute, M4I, Maastricht University, 6229 ER Maastricht, The Netherlands.
Ron M A
RM
Heeren
†Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, 7522 NB Enschede, The Netherlands.
Marcel
M
Karperien
D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008055:Lipids / Q000032:analysis* / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000737:chemistry* / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015999:Multivariate Analysis; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D018629:Spectrometry, Mass, Secondary Ion; D013997:Time Factors
D008055:Lipids; D010100:Oxygen