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Updated: Sep 4, 2025

Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
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.
Background:
In tissue engineering, mesenchymal stem cells (MSCs) are common seed cells because of abundant sources, strong proliferation ability and immunomodulatory function. Numerous researches have demonstrated that MSC-macrophage crosstalk played a key role in the tissue engineering. Macrophages could regulate the differentiation of MSCs via different molecular mechanisms, including extracellular vesicles. Apoptotic macrophages could generate large amounts of apoptotic vesicles (apoVs). ApoVs are rich in proteins, RNA (microRNAs, mRNAs, ncRNAs, etc.) and lipids, and are a key intercellular communication mediator that can exert different regulatory effects on recipient cells. MiRNAs account for about half of the total RNAs of extracellular vesicles, and play important roles in biological processes such as cell proliferation and differentiation, whereas the functions of macrophage-derived apoVs remain largely unknown. There was no research to clarify the role of macrophage-derived apoVs in MSC fate choices. In this study, we aimed to characterize macrophage-derived apoVs, and investigate the roles of macrophage-derived apoVs in the fate commitment of MSCs.
Methods:
We characterized macrophage-derived apoVs, and investigated their role in MSC osteogenesis and adipogenesis in vitro and in vivo. Furthermore, we performed microRNA loss- and gain-of-function experiments and western blot to determine the molecular mechanism.
Results:
Macrophages could produce a large number of apoVs after apoptosis. MSCs could uptake apoVs. Then, we found that macrophage-derived apoVs inhibited osteogenesis and promoted adipogenesis of MSCs in vitro and in vivo. In mechanism, apoVs were enriched for microRNA155 (miR155), and apoVs regulated osteogenesis and adipogenesis of MSCs by delivering miR155. Besides, miR155 regulated osteogenesis and adipogenesis of MSCs cultured with macrophage-derived apoVs via the SMAD2 signaling pathway.
Conclusions:
Macrophage-derived apoVs could regulate the osteogenesis and adipogenesis of MSCs through delivering miR155, which provided novel insights for MSC-mediated tissue engineering.
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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