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Isolation, Culture, and Differentiation of Bone Marrow Stromal Cells and Osteoclast Progenitors from Mice
Published on: January 6, 2018
Aging bone marrow mesenchymal stromal cells have altered membrane glycerophospholipid composition and functionality
Lotta Kilpinen1, Feven Tigistu-Sahle2, Sofia Oja3
1Advanced Therapies and Product Development, Finnish Red Cross Blood Service, Helsinki, Finland.
Journal of Lipid Research
|December 29, 2012
Summary
Extensive expansion of human bone marrow mesenchymal stem/stromal cells (hMSC) alters membrane lipids, impacting their function. Cell passaging changes glycerophospholipid profiles, reducing immunosuppressive capacity in hMSCs.
Area of Science:
- Lipidomics
- Cellular Therapy
- Immunology
Background:
- Human mesenchymal stem/stromal cells (hMSC) are vital for cellular therapies, requiring extensive expansion.
- Membrane glycerophospholipids (GPL) are precursors to signaling lipids that regulate cell functions.
- Donor age and cell doublings can influence hMSC properties.
Purpose of the Study:
- To investigate the impact of donor age and cell expansion on the glycerophospholipid (GPL) profile of human bone marrow MSC (hBMSC).
- To correlate changes in GPL and fatty acid (FA) composition with hBMSC functionality, specifically immunosuppressive capacity.
Main Methods:
- Analysis of GPL composition in hBMSCs from young and old donors at different passage numbers.
- Quantification of lipid classes, species, and acyl chains, including fatty acid profiling.
- Assessment of gene expression for enzymes involved in lipid metabolism and immunomodulation.
Main Results:
- Cell expansion significantly altered GPL composition, including an increased phosphatidylinositol to phosphatidylserine ratio.
- Accumulation of 20:4n-6 species and decrease in monounsaturated FA species were observed during passaging.
- Increased 20:4n-6 and decreased n-3 polyunsaturated FAs (e.g., 22:6n-3) in the total FA pool correlated with reduced immunosuppressive capacity.
- Changes in lipid profiles were associated with altered gene expression of lipid metabolism and immunomodulation enzymes.
Conclusions:
- Extensive expansion of hBMSCs detrimentally affects membrane GPL composition and fatty acid profiles.
- These lipid alterations negatively impact hMSC lipid signaling pathways and impair their immunosuppressive functionality.
- Findings highlight the need to consider cell expansion effects on hMSC quality for therapeutic applications.
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