Paracrine-mediated rejuvenation of aged mesenchymal stem cells is associated with downregulation of the autophagy-lysosomal pathway.
Journal
npj aging
ISSN: 2731-6068
Titre abrégé: NPJ Aging
Pays: England
ID NLM: 9918402285106676
Informations de publication
Date de publication:
18 Jul 2022
18 Jul 2022
Historique:
received:
17
10
2021
accepted:
30
06
2022
entrez:
4
8
2022
pubmed:
5
8
2022
medline:
5
8
2022
Statut:
epublish
Résumé
Age-related differences in stem-cell potency contribute to variable outcomes in clinical stem cell trials. To help understand the effect of age on stem cell potency, bone marrow-derived mesenchymal stem cells (MSCs) were isolated from young (6 weeks) and old (18-24 months) mice. HUVEC tubule formation (TF) induced by the old and young MSCs and ELISA of conditioned media were compared to one another, and to old MSCs after 7 d in indirect co-culture with young MSCs. Old MSCs induced less TF than did young (1.56 ± 0.11 vs 2.38 ± 0.17, p = 0.0003) and released lower amounts of VEGF (p = 0.009) and IGF1 (p = 0.037). After 7 d in co-culture with young MSCs, TF by the old MSCs significantly improved (to 2.09 ± 0.18 from 1.56 ± 0.11; p = 0.013), and was no longer different compared to TF from young MSCs (2.09 ± 0.18 vs 2.38 ± 0.17; p = 0.27). RNA seq of old MSCs, young MSCs, and old MSCs following co-culture with young MSCs revealed that the age-related differences were broadly modified by co-culture, with the most significant changes associated with lysosomal pathways. These results indicate that the age-associated decreased paracrine-mediated effects of old MSCs are improved following indirect co-culture with young MSC. The observed effect is associated with broad transcriptional modification, suggesting potential targets to both assess and improve the therapeutic potency of stem cells from older patients.
Identifiants
pubmed: 35927427
doi: 10.1038/s41514-022-00091-0
pii: 10.1038/s41514-022-00091-0
pmc: PMC9293998
doi:
Types de publication
Journal Article
Langues
eng
Pagination
10Informations de copyright
© 2022. The Author(s).
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