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Updated: Feb 22, 2026
Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
Membrane particles generated from mesenchymal stromal cells modulate immune responses by selective targeting of
Fabiany da C Gonçalves1,2, Franka Luk3, Sander S Korevaar3
1Graduate Program in Gastroenterology and Hepatology Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Abstract:
Mesenchymal stromal cells (MSC) are a promising therapy for immunological disorders. However, culture expanded MSC are large and get trapped in the capillary networks of the lungs after intravenous infusion, where they have a short survival time. Hypothetically, living cells are a risk for tumor formation. To reduce risks associated with MSC infusion and improve the distribution in the body, we generated membrane particles (MP) of MSC and MSC stimulated with IFN-γ (MPγ). Tracking analysis and electron microscopy indicated that the average size of MP was 120 nm, and they showed a round shape. MP exhibited ATPase, nucleotidase and esterase activity, indicating they are enzymatically active. MP and MPγ did not physically interact with T cells and had no effect on CD4+ and CD8+ T cells proliferation. However, MP and MPγ selectively bound to monocytes and decreased the frequency of pro-inflammatory CD14+CD16+ monocytes by induction of selective apoptosis. MP and MPγ increased the percentage of CD90 positive monocytes, and MPγ but not MP increased the percentage of anti-inflammatory PD-L1 monocytes. MPγ increased mRNA expression of PD-L1 in monocytes. These data demonstrate that MP have immunomodulatory properties and have potential as a novel cell-free therapy for treatment of immunological disorders.
Insights
Mesenchymal stromal cell (MSC) membrane particles (MP) offer a cell-free therapy for immune disorders. These particles modulate monocytes, reducing inflammation without affecting T cells, presenting a safer alternative to cell-based therapies.
Area of Science:
- Immunology
- Cell Biology
- Biotechnology
Background:
- Mesenchymal stromal cells (MSC) show promise for immunological disorders but face challenges with intravenous infusion, including lung trapping and short survival.
- The risk of tumor formation with living MSC necessitates exploring safer therapeutic alternatives.
Purpose of the Study:
- To investigate the therapeutic potential of MSC-derived membrane particles (MP) and IFN-γ-stimulated MP (MPγ) as a cell-free therapy.
- To evaluate the immunomodulatory effects of MP and MPγ on immune cells, particularly T cells and monocytes.
Main Methods:
- Generation and characterization of MP and MPγ, including size, shape, and enzymatic activity analysis.
- Assessment of MP and MPγ interactions with T cells (CD4+, CD8+) and monocytes (CD14+, CD16+) using flow cytometry.
- Evaluation of MP and MPγ effects on monocyte apoptosis, CD90 expression, and PD-L1 expression (mRNA and protein levels).
Main Results:
- MP and MPγ are small (approx. 120 nm), enzymatically active particles with no adverse effects on T cell proliferation.
- MP and MPγ selectively bind to monocytes, reducing pro-inflammatory CD14+CD16+ monocytes via apoptosis induction.
- MPγ significantly increases the expression of anti-inflammatory PD-L1 in monocytes, while both MP and MPγ increase CD90+ monocytes.
Conclusions:
- MSC-derived membrane particles (MP and MPγ) possess significant immunomodulatory properties.
- MP represent a promising cell-free therapeutic strategy for immunological disorders, overcoming limitations of traditional MSC therapy.
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