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Updated: Apr 28, 2026
Proteomic Analysis of Human Macrophage Polarization Under a Low Oxygen Environment
Published on: January 7, 2019
Exosomes from SHED-MSC regulate polarization and stress oxidative indexes in THP-1 derived M1 macrophages
Ali Fallah1, Abasalt Hosseinzadeh Colagar1, Ayyoob Khosravi2
1Molecular and Cell Biology Department, Faculty of Basic Science, University of Mazandaran, Babolsar, 47416-95447, Iran.
Objective:
The inhibition of M1 macrophages may be interesting for targeted therapy with mesenchymal stem cell-derived Exosomes (MSC-EXOs). This study aimed to investigate the stem cells of human exfoliated deciduous teeth-derived EXOs (SHED-MSC-EXOs) effect on regulating the pro- and anti-oxidant indexes and inhibiting M1 macrophage polarization. Besides, an in-silico analysis of SHED-MSC-EXO miRNAs as the highest frequency of small RNAs in the exosomes was performed to discover the possible mechanism.
Methods:
The flow cytometry analysis of CD80 and CD86 as M1-specific markers confirmed the polarization of macrophages derived from THP-1 cells. After exosome isolation, characterization, and internalization, THP-1-derived M1 macrophages were treated with SHED-MSC-EXOs. M1-specific markers and pro- and anti-oxidant indexes were evaluated. For in-silico analysis of SHED-MSC-EXOs miRNAs, initial miRNA array data of SHED-EXOs is collected from GEO, and the interaction of the miRNAs in M1 macrophage polarization (M1P), mitochondrial oxidative stress (MOS) and LPS-induced oxidative stress (LOS) were analyzed by miRWalk 3.0 server. Outcomes were filtered by 75th percentile signal intensity, score cut-off ≥0.95, minimum free energy (MEF)≤ -20 kcal/mol, and seed = 1.
Results:
It shows a decrease in the expression of CD80 and CD81, a reduction in pro-oxidant indicators, and an increase in the anti-oxidant indexes (P < 0.05). Computational analysis showed that eight microRNAs of SHED-MSC-EXO miRNAs can bind to and interfere with the expression of candidate genes in the M1P, MOS, and LOS pathways simultaneously.
Conclusion:
SHED-MSCs-EXOs can be utilized to treat conditions related to M1 macrophage-induced diseases (M1IDs) due to their unique physical properties and ability to penetrate target cells easily.
Insights
Mesenchymal stem cell-derived exosomes (MSC-EXOs) from deciduous teeth (SHED-MSC-EXOs) can regulate oxidative stress and inhibit M1 macrophage polarization. These findings suggest SHED-MSC-EXOs hold potential for treating M1 macrophage-induced diseases.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Immunology
Background:
- M1 macrophages play a crucial role in inflammatory diseases.
- Mesenchymal stem cell-derived exosomes (MSC-EXOs) are investigated for therapeutic potential.
- Inhibition of M1 macrophages is a target for novel therapies.
Purpose of the Study:
- To investigate the therapeutic effects of stem cells from human exfoliated deciduous teeth-derived exosomes (SHED-MSC-EXOs) on M1 macrophage polarization.
- To evaluate the impact of SHED-MSC-EXOs on pro- and anti-oxidant indexes.
- To elucidate the underlying molecular mechanisms through in-silico analysis of SHED-MSC-EXO miRNAs.
Main Methods:
- THP-1 derived M1 macrophages were treated with isolated and characterized SHED-MSC-EXOs.
- Flow cytometry was used to analyze M1-specific markers (CD80, CD86).
- Pro- and anti-oxidant indexes were measured; in-silico miRNA analysis was performed using miRWalk 3.0.
Main Results:
- SHED-MSC-EXOs treatment significantly decreased M1 macrophage markers (CD80, CD81).
- Treatment led to reduced pro-oxidant and increased anti-oxidant indexes (P < 0.05).
- In-silico analysis identified eight SHED-MSC-EXO miRNAs capable of targeting M1 polarization, mitochondrial, and LPS-induced oxidative stress pathways.
Conclusions:
- SHED-MSC-EXOs effectively inhibit M1 macrophage polarization and modulate oxidative stress.
- These exosomes demonstrate potential as a therapeutic agent for M1 macrophage-related diseases (M1IDs).
- The ability of SHED-MSC-EXOs to penetrate target cells makes them promising for clinical applications.
