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



Turlo, Agnieszka J ORCID: 0000-0003-0608-9504, Hammond, Dean E, Ramsbottom, Kerry A, Soul, Jamie ORCID: 0000-0003-2255-6459, Gillen, Alexandra ORCID: 0000-0003-2291-6389, McDonald, Kieran and Peffers, Mandy J ORCID: 0000-0001-6979-0440
(2023) Mesenchymal Stromal Cell Secretome Is Affected by Tissue Source and Donor Age. Stem cells (Dayton, Ohio), 41 (11). pp. 1047-1059.

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Abstract

Variation in mesenchymal stromal cell (MSC) function depending on their origin is problematic, as it may confound clinical outcomes of MSC therapy. Current evidence suggests that the therapeutic benefits of MSCs are attributed to secretion of biologically active factors (secretome). However, the effect of donor characteristics on the MSC secretome remains largely unknown. Here, we examined the influence of donor age, sex, and tissue source, on the protein profile of the equine MSC secretome. We used dynamic metabolic labeling with stable isotopes combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify secreted proteins in MSC conditioned media (CM). Seventy proteins were classified as classically secreted based on the rate of label incorporation into newly synthesized proteins released into the extracellular space. Next, we analyzed CM of bone marrow- (n = 14) and adipose-derived MSCs (n = 16) with label-free LC-MS/MS. Clustering analysis of 314 proteins detected across all samples identified tissue source as the main factor driving variability in MSC CM proteomes. Linear modelling applied to the subset of 70 secreted proteins identified tissue-related difference in the abundance of 23 proteins. There was an age-related decrease in the abundance of CTHRC1 and LOX, further validated with orthogonal techniques. Due to the lack of flow cytometry characterization of MSC surface markers, the analysis could not account for the potential effect of cell population heterogeneity. This study provides evidence that tissue source and donor age contribute to differences in the protein composition of MSC secretomes which may influence the effects of MSC therapy.

Item Type: Article
Uncontrolled Keywords: Mesenchymal Stem Cells, Bone Marrow, Animals, Horses, Culture Media, Conditioned, Chromatography, Liquid, Tandem Mass Spectrometry, Secretome
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 21 Aug 2023 07:44
Last Modified: 18 Nov 2023 02:06
DOI: 10.1093/stmcls/sxad060
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3172243