Differentiation of Mesenchymal Stem Cells under Hypoxia and Normoxia: Lipid Profiles Revealed by Time-of-Flight Secondary Ion Mass Spectrometry and Multivariate Analysis

Nicole Georgi, B. Cillero Pastor, G.B. Eijkel, P.C. Periyasamy, A. Kiss, Clemens van Blitterswijk, Janine Nicole Post, R.M.A. Heeren, Hermanus Bernardus Johannes Karperien

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Abstract

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.
Original languageEnglish
Pages (from-to)3981-3988
Number of pages8
JournalAnalytical chemistry
Volume87
Issue number7
DOIs
Publication statusPublished - 5 Mar 2015

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Secondary ion mass spectrometry
Stem cells
Fibroblast Growth Factor 1
Oxygen
Lipids
Cholesterol
Cartilage
Discriminant analysis
Pathology
Cell culture
Gene expression
Principal component analysis
Labels
Multivariate Analysis

Keywords

  • METIS-310543
  • IR-95939

Cite this

Georgi, Nicole ; Cillero Pastor, B. ; Eijkel, G.B. ; Periyasamy, P.C. ; Kiss, A. ; van Blitterswijk, Clemens ; Post, Janine Nicole ; Heeren, R.M.A. ; Karperien, Hermanus Bernardus Johannes. / Differentiation of Mesenchymal Stem Cells under Hypoxia and Normoxia: Lipid Profiles Revealed by Time-of-Flight Secondary Ion Mass Spectrometry and Multivariate Analysis. In: Analytical chemistry. 2015 ; Vol. 87, No. 7. pp. 3981-3988.
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abstract = "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.",
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Differentiation of Mesenchymal Stem Cells under Hypoxia and Normoxia: Lipid Profiles Revealed by Time-of-Flight Secondary Ion Mass Spectrometry and Multivariate Analysis. / Georgi, Nicole; Cillero Pastor, B.; Eijkel, G.B.; Periyasamy, P.C.; Kiss, A.; van Blitterswijk, Clemens; Post, Janine Nicole; Heeren, R.M.A.; Karperien, Hermanus Bernardus Johannes.

In: Analytical chemistry, Vol. 87, No. 7, 05.03.2015, p. 3981-3988.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Georgi, Nicole

AU - Cillero Pastor, B.

AU - Eijkel, G.B.

AU - Periyasamy, P.C.

AU - Kiss, A.

AU - van Blitterswijk, Clemens

AU - Post, Janine Nicole

AU - Heeren, R.M.A.

AU - Karperien, Hermanus Bernardus Johannes

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N2 - 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.

AB - 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.

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