Mesenchymal Stromal Cell Secretome Is Affected by Tissue Source and Donor Age.
age
donor
equine
mesenchymal stromal cells
proteomics
secretome
Journal
Stem cells (Dayton, Ohio)
ISSN: 1549-4918
Titre abrégé: Stem Cells
Pays: England
ID NLM: 9304532
Informations de publication
Date de publication:
05 Nov 2023
05 Nov 2023
Historique:
received:
15
02
2023
accepted:
21
07
2023
medline:
10
11
2023
pubmed:
18
8
2023
entrez:
17
8
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37591507
pii: 7244687
doi: 10.1093/stmcls/sxad060
pmc: PMC10631804
doi:
Substances chimiques
Culture Media, Conditioned
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1047-1059Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press.
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