Abstract
Mesenchymal stem cells (MSC) are currently being tested clinically for a plethora of conditions, with most approaches relying on the secretion of paracrine signals by MSC to modulate the immune system, promote wound healing, and induce angiogenesis. Hypoxia has been shown to affect MSC proliferation, differentiation, survival and secretory profile. Here, we investigate changes in the lipid composition of human bone marrow-derived MSC after exposure to hypoxia. Using mass spectrometry, we compared the lipid profiles of MSC derived from five different donors, cultured for two days in either normoxia (control) or hypoxia (1% oxygen). Hypoxia induced a significant increase of total triglycerides, fatty acids and diacylglycerols (DG). Remarkably, reduction of DG levels using the phosphatidylcholine-specific phospholipase C inhibitor D609 inhibited the secretion of VEGF and Angiopoietin-2, but increased the secretion of interleukin-8, without affecting significantly their respective mRNA levels. Functionally, incubation of MSC in hypoxia with D609 inhibited the potential of the cells to promote migration of human endothelial cells in a wound/scratch assay. Hence, we show that hypoxia induces in MSC an increase of DG that may affect the angiogenic potential of these cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 300-307 |
| Number of pages | 8 |
| Journal | Journal of Cellular Biochemistry |
| Volume | 117 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2016 |
Fingerprint
Keywords
- DIACYLGLYCEROLS
- HYPOXIA
- MESENCHYMAL STEM CELLS
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Mesenchymal Stem Cells Respond to Hypoxia by Increasing Diacylglycerols. / Lakatos, Kinga; Kalomoiris, Stefanos; Merkely, Béla; Nolta, Jan; Fierro, Fernando A.
In: Journal of Cellular Biochemistry, Vol. 117, No. 2, 01.02.2016, p. 300-307.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mesenchymal Stem Cells Respond to Hypoxia by Increasing Diacylglycerols
AU - Lakatos, Kinga
AU - Kalomoiris, Stefanos
AU - Merkely, Béla
AU - Nolta, Jan
AU - Fierro, Fernando A
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Mesenchymal stem cells (MSC) are currently being tested clinically for a plethora of conditions, with most approaches relying on the secretion of paracrine signals by MSC to modulate the immune system, promote wound healing, and induce angiogenesis. Hypoxia has been shown to affect MSC proliferation, differentiation, survival and secretory profile. Here, we investigate changes in the lipid composition of human bone marrow-derived MSC after exposure to hypoxia. Using mass spectrometry, we compared the lipid profiles of MSC derived from five different donors, cultured for two days in either normoxia (control) or hypoxia (1% oxygen). Hypoxia induced a significant increase of total triglycerides, fatty acids and diacylglycerols (DG). Remarkably, reduction of DG levels using the phosphatidylcholine-specific phospholipase C inhibitor D609 inhibited the secretion of VEGF and Angiopoietin-2, but increased the secretion of interleukin-8, without affecting significantly their respective mRNA levels. Functionally, incubation of MSC in hypoxia with D609 inhibited the potential of the cells to promote migration of human endothelial cells in a wound/scratch assay. Hence, we show that hypoxia induces in MSC an increase of DG that may affect the angiogenic potential of these cells.
AB - Mesenchymal stem cells (MSC) are currently being tested clinically for a plethora of conditions, with most approaches relying on the secretion of paracrine signals by MSC to modulate the immune system, promote wound healing, and induce angiogenesis. Hypoxia has been shown to affect MSC proliferation, differentiation, survival and secretory profile. Here, we investigate changes in the lipid composition of human bone marrow-derived MSC after exposure to hypoxia. Using mass spectrometry, we compared the lipid profiles of MSC derived from five different donors, cultured for two days in either normoxia (control) or hypoxia (1% oxygen). Hypoxia induced a significant increase of total triglycerides, fatty acids and diacylglycerols (DG). Remarkably, reduction of DG levels using the phosphatidylcholine-specific phospholipase C inhibitor D609 inhibited the secretion of VEGF and Angiopoietin-2, but increased the secretion of interleukin-8, without affecting significantly their respective mRNA levels. Functionally, incubation of MSC in hypoxia with D609 inhibited the potential of the cells to promote migration of human endothelial cells in a wound/scratch assay. Hence, we show that hypoxia induces in MSC an increase of DG that may affect the angiogenic potential of these cells.
KW - DIACYLGLYCEROLS
KW - HYPOXIA
KW - MESENCHYMAL STEM CELLS
UR - http://www.scopus.com/inward/record.url?scp=84957308925&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84957308925&partnerID=8YFLogxK
U2 - 10.1002/jcb.25292
DO - 10.1002/jcb.25292
M3 - Article
C2 - 26212931
AN - SCOPUS:84957308925
VL - 117
SP - 300
EP - 307
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
SN - 0730-2312
IS - 2
ER -