Adipose-derived mesenchymal stem cells release microvesicles with procoagulant activity

Tomas Fiedler1, Magdalena Rabe2, Ralf G Mundkowski3

  • 1Institute of Medical Microbiology, Virology, and Hygiene, Rostock University Medical Centre, Schillingallee 70, 18057 Rostock, Germany.

Insights

Mesenchymal stromal/stem cell (MSC)-derived extracellular vesicles show procoagulant activity. This activity is independent of inflammatory stimulation, suggesting a consistent therapeutic potential for these vesicles in coagulation-related applications.

Area of Science:

  • Cell biology
  • Biochemistry
  • Biomedical engineering

Background:

  • Extracellular vesicles (EVs) from mesenchymal stromal/stem cells (MSC) mimic cellular therapeutic effects.
  • Adipose-derived MSC (adMSC) are a source of MSCs with therapeutic potential.

Purpose of the Study:

  • To characterize EVs produced by adipose-derived MSC (adMSC).
  • To investigate the effect of inflammatory stimulation (lipopolysaccharide and tumor necrosis factor) on adMSC-EV production and function.
  • To determine the procoagulant activity of adMSC-EVs and the underlying coagulation pathways involved.

Main Methods:

  • Isolation and characterization of extracellular vesicles from adipose-derived MSCs.
  • In vitro stimulation of adMSCs with lipopolysaccharide (LPS) and tumor necrosis factor (TNF).
  • Assessment of EV production quantity.
  • Evaluation of EV procoagulant activity using coagulation assays.
  • Analysis of intrinsic and extrinsic coagulation pathway involvement.

Main Results:

  • Inflammatory stimulation with LPS and TNF did not alter the number of EVs produced by adMSCs.
  • adMSC-derived EVs exhibited significant procoagulant activity.
  • This procoagulant activity was observed regardless of prior inflammatory stimulation.
  • Evidence suggests that adMSC-EVs activate both the intrinsic and extrinsic pathways of coagulation.

Conclusions:

  • Adipose-derived MSC-derived extracellular vesicles possess inherent procoagulant properties.
  • The procoagulant activity of these EVs is consistent and not dependent on inflammatory priming.
  • adMSC-EVs activate coagulation through both intrinsic and extrinsic pathways.
  • These findings highlight the potential of adMSC-EVs as therapeutic agents in hemostasis and thrombosis.

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