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Published on: November 18, 2009

SLFN11 binds DDX1 to counteract human mesenchymal stem/stromal cell senescence through inhibition of mTOR/eIF4E

Xin-Xin Zhu1, Yi Luo1, Jin-Yan Xu2

  • 1Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China; Guizhou Provincial Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine in Colleges and Universities, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China; Zunyi Municipal Key Laboratory of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China.

Life Sciences
|July 6, 2026
PubMed
Abstract

Insights

Schlafen (SLFN) 11 gene protects mesenchymal stem/stromal cells (MSCs) from senescence by targeting DDX1/mTOR/eIF4E signaling. SLFN11-engineered MSCs show enhanced therapeutic efficacy and safety for cell therapy.

Area of Science:

  • Cell Biology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Mesenchymal stem/stromal cells (MSCs) are crucial for cellular therapy.
  • In vitro expansion leads to MSC senescence, reducing stemness and therapeutic potential.

Purpose of the Study:

  • Investigate the protective role of the Schlafen (SLFN) 11 gene against human MSC senescence.
  • Elucidate the mechanism of SLFN11 in preventing senescence.
  • Evaluate the efficacy and safety of SLFN11-overexpressing MSCs for therapeutic applications.

Main Methods:

  • Overexpressed SLFN11 in human MSCs using lentiviral transduction.
  • Assessed senescence markers, including cell cycle arrest, proliferation, DNA damage, and β-galactosidase activity.
  • Utilized co-immunoprecipitation and LC-MS/MS to identify molecular interactions.
  • Evaluated therapeutic efficacy in a DSS-induced ulcerative colitis mouse model.

Main Results:

  • SLFN11 overexpression attenuated MSC senescence, enhancing proliferation, clonogenicity, and stemness.
  • SLFN11 bound DDX1, inhibiting mTOR/eIF4E signaling to resist senescence.
  • SLFN11-engineered MSCs demonstrated superior protection against ulcerative colitis in mice.
  • No detectable tumorigenicity or chromosomal aberrations were observed in SLFN11-overexpressing MSCs.

Conclusions:

  • SLFN11 plays a novel role in protecting MSCs from senescence through the DDX1/mTOR/eIF4E pathway.
  • SLFN11-overexpressing MSCs represent a promising and safe cell source for therapy with preserved pluripotency and enhanced efficacy.
Keywords:
Cell therapyCelluar senescenceDDX1/mTOR/eIF4E signaling axisSLFN11

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