2021 Volume No 42 – pages 401-414
Title: TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells |
Authors: C Voskamp, LA Anderson, WJLM Koevoet, S Barnhoorn, PG Mastroberardino, GJVM van Osch, R Narcisi |
Address: Department of Orthopaedics and Sports Medicine, Erasmus MC, 3015 CN Rotterdam, the Netherlands |
E-mail: r.narcisi at erasmusmc.nl |
Abstract: Mesenchymal stem cells (MSCs) are promising cells for regenerative medicine therapies because they can differentiate towards multiple cell lineages. However, the occurrence of cellular senescence and the acquiring of the senescence-associated secretory phenotype (SASP) limit their clinical use. Since the transcription factor TWIST1 influences expansion of MSCs, its role in regulating cellular senescence was investigated. The present study demonstrated that silencing of TWIST1 in MSCs increased the occurrence of senescence, characterised by a SASP profile different from irradiation-induced senescent MSCs. Knowing that senescence alters cellular metabolism, cellular bioenergetics was monitored by using the Seahorse XF apparatus. Both TWIST1-silencing-induced and irradiation-induced senescent MSCs had a higher oxygen consumption rate compared to control MSCs, while TWIST1-silencing-induced senescent MSCs had a low extracellular acidification rate compared to irradiation-induced senescent MSCs. Overall, data indicated how TWIST1 regulation influenced senescence in MSCs and that TWIST1 silencing-induced senescence was characterised by a specific SASP profile and metabolic state. |
Key Words: Mesenchymal stem cells, cellular senescence, secretory phenotype, regenerative medicine, metabolism.
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Publication date: November 25th 2021 |
Article download: Pages 401-414 (PDF file) |
