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

Frontiers in Bioengineering and Biotechnology

Bioengineering and Biotechnology

Chantal Voskamp¹  Roberto Narcisi¹  Gerjo J. V. M. Van Osch²  Wendy J. L. M. Koevoet³ 

[1]Department of Orthopaedics and Sports Medicine, University Medical Center Rotterdam, Rotterdam, Netherlands

[2]Department of Orthopaedics and Sports Medicine, University Medical Center Rotterdam, Rotterdam, Netherlands

[3]Department of Otorhinolaryngology, University Medical Center Rotterdam, Rotterdam, Netherlands

[4]Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, Netherlands

[5]Department of Otorhinolaryngology, University Medical Center Rotterdam, Rotterdam, Netherlands

关键词: senescence;    cartilage;    MSC;    chondrogenesis;    SASP;    regenerative medicine;    tissue engineering;    TGFβ;   

DOI  :  10.3389/fbioe.2023.1241338

 received in 2023-06-16, accepted in 2023-07-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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