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TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells

C Voskamp, L A Anderson, W J Koevoet

  • 1Department of Orthopaedics and Sports Medicine, Erasmus MC, 3015 CN Rotterdam, the Netherlands.r.narcisi@erasmusmc.nl.

European Cells & Materials
|November 26, 2021
PubMed

Insights

Silencing TWIST1 in mesenchymal stem cells (MSCs) accelerates senescence and alters their metabolic profile, impacting regenerative medicine potential. This specific senescence differs from irradiation-induced aging.

Area of Science:

  • Cell Biology
  • Regenerative Medicine
  • Stem Cell Biology

Background:

  • Mesenchymal stem cells (MSCs) hold promise for regenerative medicine due to their differentiation potential.
  • Cellular senescence and the senescence-associated secretory phenotype (SASP) impede the clinical application of MSCs.
  • The transcription factor TWIST1 is known to influence MSC expansion.

Purpose of the Study:

  • To investigate the role of TWIST1 in regulating cellular senescence in MSCs.
  • To characterize the senescence-associated secretory phenotype (SASP) and metabolic state of TWIST1-silencing-induced senescent MSCs.

Main Methods:

  • Silencing of the TWIST1 gene in MSCs.
  • Characterization of senescence markers and SASP profiles.
  • Assessment of cellular bioenergetics using Seahorse XF analysis.

Main Results:

  • TWIST1 silencing significantly increased senescence occurrence in MSCs.
  • TWIST1-silencing-induced senescence exhibited a distinct SASP profile compared to irradiation-induced senescence.
  • Both TWIST1-silencing-induced and irradiation-induced senescent MSCs showed elevated oxygen consumption rates.
  • TWIST1-silencing-induced senescent MSCs displayed a lower extracellular acidification rate than irradiation-induced senescent MSCs.

Conclusions:

  • TWIST1 plays a crucial role in regulating senescence in MSCs.
  • TWIST1 silencing induces a unique form of senescence with a specific SASP and metabolic signature.
  • Understanding TWIST1's role in MSC senescence is vital for advancing regenerative medicine therapies.

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