Department of Orthopaedics and Sports Medicine, Erasmus MC, 3015 CN Rotterdam, the
Eur Cell Mater. 2021 Nov 25;42:401-414. doi: 10.22203/eCM.v042a25.
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.
间充质干细胞（MSCs）是再生医学治疗中很有前途的细胞，因为它们可以向多种细胞谱系分化。然而，细胞衰老的发生和衰老相关分泌表型（SASP）的获得限制了它们的临床应用。由于转录因子 TWIST1 影响 MSCs 的扩增，因此研究了其在调节细胞衰老中的作用。本研究表明，沉默 MSCs 中的 TWIST1 会增加衰老的发生，其 SASP 特征与辐射诱导的衰老 MSCs 不同。由于衰老改变了细胞代谢，本研究使用 Seahorse XF 仪器监测细胞生物能量学。与对照 MSCs 相比，TWIST1 沉默诱导的衰老 MSCs 和辐射诱导的衰老 MSCs 的耗氧率更高，而 TWIST1 沉默诱导的衰老 MSCs 的细胞外酸化率比辐射诱导的衰老 MSCs 低。总的来说，数据表明 TWIST1 调节如何影响 MSCs 中的衰老，并且 TWIST1 沉默诱导的衰老表现出特定的 SASP 特征和代谢状态。
