Senescence during early differentiation reduced the chondrogenic differentiation capacity of mesenchymal progenitor cells

Chantal Voskamp, Wendy J.L.M. Koevoet, Gerjo J.V.M. Van Osch*, Roberto Narcisi*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Introduction: 

Mesenchymal stromal/progenitor cells (MSCs) are promising for cartilage cell-based therapies due to their chondrogenic differentiation capacity. However, MSCs can become senescent during in vitro expansion, a state characterized by stable cell cycle arrest, metabolic alterations, and substantial changes in the gene expression and secretory profile of the cell. In this study, we aimed to investigate how senescence and the senescence-associated secretory phenotype (SASP) affect chondrogenic differentiation of MSCs. 

Methods: 

To study the effect of senescence, we exposed MSCs to gamma irradiation during expansion or during chondrogenic differentiation (the pellet culture). Western blot analysis was used to evaluate MSCs response to the chondrogenic inductor TGF-β. 

Results: 

When senescence was induced during expansion or at day 7 of chondrogenic differentiation, we observed a significant reduction in the cartilage matrix. Interestingly, when senescence was induced at day 14 of differentiation, chondrogenesis was not significantly altered. Moreover, exposing chondrogenic pellets to the medium conditioned by senescent pellets had no significant effect on the expression of anabolic or catabolic cartilage markers, suggesting a neglectable paracrine effect of senescence on cartilage generation in our model. Finally, we show that senescent MSCs showed lower phosphorylated SMAD2 levels after TGFβ1 stimulation than control MSCs. 

Conclusion: 

Overall, these results suggest that the occurrence of senescence in MSCs during expansion or early differentiation could be detrimental for cartilage tissue engineering.

Original languageEnglish
Article number1241338
JournalFrontiers in Bioengineering and Biotechnology
Volume11
DOIs
Publication statusPublished - 7 Aug 2023

Bibliographical note

Funding Information:
This research was financially supported by the Dutch Arthritis Society (ReumaNederland; 16-1-201) and by a TTW Perspectief grant from NWO (William Hunter Revisited; P15-23). This study is part of the Medical Delta RegMed4D program.

Publisher Copyright:
Copyright © 2023 Voskamp, Koevoet, Van Osch and Narcisi.

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