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Updated: Sep 25, 2025

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Electrostatic Charge-Mediated Apoptotic Vesicle Biodistribution Attenuates Sepsis by Switching Neutrophil NETosis to

Qianmin Ou1, Lingping Tan1, Yiting Shao1

  • 1South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, 510080, P. R. China.

Small (Weinheim an Der Bergstrasse, Germany)
|April 28, 2022
PubMed

Insights

Mesenchymal stem cell-derived apoptotic vesicles (apoVs) treat sepsis by targeting neutrophils in bone marrow. ApoVs induce neutrophil apoptosis via electrostatic interactions and the Fas pathway, improving survival in septic mice.

Area of Science:

  • Immunology
  • Cell Biology
  • Regenerative Medicine

Background:

  • Sepsis causes organ damage and mortality.
  • Mesenchymal stem cell (MSC) therapy shows promise in sepsis treatment.
  • The precise mechanisms of MSC therapy in sepsis remain unclear.

Purpose of the Study:

  • To investigate the therapeutic potential of MSC-derived apoptotic vesicles (apoVs) in sepsis.
  • To elucidate the underlying mechanisms of apoV action in sepsis treatment.

Main Methods:

  • Septic mouse model.
  • Tail vein infusion of apoVs.
  • Analysis of apoV distribution and interaction with neutrophils.
  • Investigation of the Fas ligand (FasL)-Fas pathway.

Main Results:

  • ApoVs ameliorated multiple organ dysfunction and improved survival in septic mice.
  • ApoVs accumulated in the bone marrow of septic mice through electrostatic interactions with neutrophil extracellular traps (NETs).
  • ApoVs induced neutrophil apoptosis by activating the apoV-FasL-Fas pathway, shifting NETosis to apoptosis.

Conclusions:

  • MSC-derived apoVs represent a novel therapeutic strategy for sepsis.
  • Electrostatic charge-directed interactions mediate apoV targeting to NETs in bone marrow.
  • The apoV-FasL-Fas pathway is crucial for the therapeutic effects of apoVs in sepsis.
Keywords:
Fas/Fas ligand pathwayapoptotic vesicleselectrostatic interactionsneutrophilssepsis

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