Mesenchymal Stromal Cell Secretome Is Affected by Tissue Source and Donor Age

Area of Science:

• Veterinary Medicine
• Cell Biology
• Proteomics

Background:

• Mesenchymal stromal cells (MSCs) show variable function based on origin, potentially affecting therapy outcomes.
• Therapeutic benefits of MSCs are linked to their secreted factors (secretome).
• The impact of donor characteristics on the MSC secretome is not well understood.

Purpose of the Study:

• To investigate how donor age, sex, and tissue source influence the protein profile of equine MSC secretomes.
• To identify specific proteins affected by these donor characteristics.

Main Methods:

• Utilized dynamic metabolic labeling with stable isotopes and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify secreted proteins.
• Analyzed conditioned media from bone marrow- and adipose-derived MSCs using label-free LC-MS/MS.
• Applied clustering and linear modeling to analyze proteomic data.

Main Results:

• Identified 70 classically secreted proteins and 314 total proteins across samples.
• Tissue source was the primary driver of variability in MSC secretomes.
• Tissue source differences were observed in 23 secreted proteins; donor age correlated with decreased CTHRC1 and LOX abundance.

Conclusions:

• Equine MSC secretome composition is significantly influenced by tissue source and donor age.
• These variations may impact the efficacy and clinical outcomes of MSC-based therapies.
• Further research is needed to understand the implications of cell population heterogeneity.