Macrophage-derived apoptotic vesicles regulate fate commitment of mesenchymal stem cells via miR155

Yuan Zhu1,2, Xiao Zhang1,2, Kunkun Yang1,2

  • 1Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Beijing, 100081, China.

Abstract

Insights

Macrophage-derived apoptotic vesicles (apoVs) inhibit bone formation and promote fat formation in mesenchymal stem cells (MSCs). This occurs via delivery of microRNA155 (miR155), offering new insights into MSC-mediated tissue engineering.

Area of Science:

  • Tissue Engineering
  • Cell Biology
  • Molecular Mechanisms

Background:

  • Mesenchymal stem cells (MSCs) are crucial in tissue engineering due to their regenerative and immunomodulatory properties.
  • MSC-macrophage interactions are vital, with macrophages influencing MSC differentiation through mechanisms like extracellular vesicles.
  • Macrophage-derived apoptotic vesicles (apoVs) are lipid- and RNA-rich mediators, but their role in MSC fate determination is largely unexplored.

Purpose of the Study:

  • To characterize macrophage-derived apoVs.
  • To investigate the role of these apoVs in the osteogenesis and adipogenesis of MSCs.
  • To elucidate the molecular mechanisms underlying apoV-mediated MSC fate regulation.

Main Methods:

  • Characterization of macrophage-derived apoVs.
  • In vitro and in vivo studies on MSC osteogenesis and adipogenesis.
  • MicroRNA loss- and gain-of-function experiments and western blot analysis.

Main Results:

  • Macrophage apoptosis yields abundant apoVs, which are taken up by MSCs.
  • Macrophage-derived apoVs were found to inhibit MSC osteogenesis and promote adipogenesis.
  • These effects were mediated by microRNA155 (miR155) delivered via apoVs, acting through the SMAD2 signaling pathway.

Conclusions:

  • Macrophage-derived apoVs regulate MSC osteogenesis and adipogenesis by delivering miR155.
  • This finding provides novel insights into the mechanisms of MSC-mediated tissue engineering.
  • The study highlights the potential of targeting apoV-miR155 interactions for therapeutic applications.

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