TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells

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. Sinc...

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Autores principales: C Voskamp, LA Anderson, WJLM Koevoet, S Barnhoorn, PG Mastroberardino, GJVM van Osch, R Narcisi
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Publicado: AO Research Institute Davos 2021
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Acceso en línea:https://doaj.org/article/b24bd650f1c143828171c2dfd52711ad
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spelling oai:doaj.org-article:b24bd650f1c143828171c2dfd52711ad2021-11-26T10:42:16ZTWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells10.22203/eCM.v042a251473-2262https://doaj.org/article/b24bd650f1c143828171c2dfd52711ad2021-11-01T00:00:00Zhttps://www.ecmjournal.org/papers/vol042/pdf/v042a25.pdfhttps://doaj.org/toc/1473-2262Mesenchymal 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.C VoskampLA AndersonWJLM KoevoetS BarnhoornPG MastroberardinoGJVM van OschR Narcisi AO Research Institute Davosarticlemesenchymal stem cellscellular senescencesecretory phenotyperegenerative medicinemetabolismSurgeryRD1-811Diseases of the musculoskeletal systemRC925-935ENEuropean Cells & Materials, Vol 42, Pp 401-414 (2021)
institution DOAJ
collection DOAJ
language EN
topic mesenchymal stem cells
cellular senescence
secretory phenotype
regenerative medicine
metabolism
Surgery
RD1-811
Diseases of the musculoskeletal system
RC925-935
spellingShingle mesenchymal stem cells
cellular senescence
secretory phenotype
regenerative medicine
metabolism
Surgery
RD1-811
Diseases of the musculoskeletal system
RC925-935
C Voskamp
LA Anderson
WJLM Koevoet
S Barnhoorn
PG Mastroberardino
GJVM van Osch
R Narcisi
TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells
description 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.
format article
author C Voskamp
LA Anderson
WJLM Koevoet
S Barnhoorn
PG Mastroberardino
GJVM van Osch
R Narcisi
author_facet C Voskamp
LA Anderson
WJLM Koevoet
S Barnhoorn
PG Mastroberardino
GJVM van Osch
R Narcisi
author_sort C Voskamp
title TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells
title_short TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells
title_full TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells
title_fullStr TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells
title_full_unstemmed TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells
title_sort twist1 controls cellular senescence and energy metabolism in mesenchymal stem cells
publisher AO Research Institute Davos
publishDate 2021
url https://doaj.org/article/b24bd650f1c143828171c2dfd52711ad
work_keys_str_mv AT cvoskamp twist1controlscellularsenescenceandenergymetabolisminmesenchymalstemcells
AT laanderson twist1controlscellularsenescenceandenergymetabolisminmesenchymalstemcells
AT wjlmkoevoet twist1controlscellularsenescenceandenergymetabolisminmesenchymalstemcells
AT sbarnhoorn twist1controlscellularsenescenceandenergymetabolisminmesenchymalstemcells
AT pgmastroberardino twist1controlscellularsenescenceandenergymetabolisminmesenchymalstemcells
AT gjvmvanosch twist1controlscellularsenescenceandenergymetabolisminmesenchymalstemcells
AT rnarcisi twist1controlscellularsenescenceandenergymetabolisminmesenchymalstemcells
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