Senescence-Induced Lipidome Alterations in Mesenchymal Stromal Cells

Area of Science:

• Cell Biology
• Biochemistry
• Metabolomics

Background:

• Mesenchymal stromal cells (MSCs) are promising for clinical applications.
• Cellular senescence limits MSC therapeutic potential and expansion.
• Understanding MSC culture dynamics is crucial for effective cell therapy.

Purpose of the Study:

• To investigate alterations in MSC lipid metabolism during culture expansion.
• To correlate lipid profiles with senescence markers in cultured MSCs.
• To identify potential lipid biomarkers for early senescence detection.

Main Methods:

• Cultured human MSCs from two donors for 12 days.
• Assessed senescence using senescence-associated β-galactosidase (SA-β-gal) activity.
• Analyzed lipid profiles using ultrahigh-performance liquid chromatography mass spectrometry (UHPLC-MS/MS).
• Identified 237 unique lipid species through spectral database matching.

Main Results:

• Lipid abundance generally increased across most classes during serial culture.
• Significant donor-to-donor heterogeneity was observed in lipid profiles.
• Twelve lipids, including four triglycerides (TGs), distinguished senescence levels (<10%, 10-20%, >20% SA-β-gal+).
• TGs with long-chain, unsaturated fatty acids correlated strongly with increased MSC senescence.

Conclusions:

• MSC lipid metabolism changes significantly during culture expansion.
• Specific lipid signatures, especially certain triglycerides, can indicate senescence.
• Lipid profiling offers a potential method for monitoring MSC culture quality and senescence.