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Matrix-bound nanovesicles as epigenetic modulators of myeloid cells
Héctor Capella-Monsonís1,2,3, Jiayang Rong1,2, Bharadwaj Chirravuri1,2
1McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Pittsburgh, PA 15219, USA.
Matrix-bound nanovesicles (MBV) alter myeloid cell epigenetics, explaining their long-lasting immune effects. These extracellular vesicles (EV) offer potential therapeutic applications by modifying cell communication and responses.
Area of Science:
- Cell Biology
- Immunology
- Epigenetics
Background:
- Extracellular vesicles (EV) mediate cell-to-cell communication.
- Matrix-bound nanovesicles (MBV), a type of EV, exhibit durable immunomodulatory effects on myeloid cells.
- The mechanism behind MBV's prolonged effects, even beyond myeloid cell lifespan, remains unclear.
Purpose of the Study:
- To investigate MBV-directed epigenetic modification in myeloid precursors.
- To explore the role of epigenetics in the sustained immunomodulatory effects of MBV.
- To understand how MBV influence myeloid cell differentiation and response.
Main Methods:
- Flow cytometry to analyze cell populations.
- ATAC sequencing to assess chromatin accessibility.
- Treatment of myeloid progenitors and differentiated macrophages with MBV.
Main Results:
- MBV are internalized by both myeloid progenitors and differentiated macrophages.
- MBV internalization induces epigenetic changes, modulating macrophage inflammatory responses.
- MBV treatment alters chromatin accessibility differently in progenitors versus macrophages.
Conclusions:
- MBV induce epigenetic modifications in myeloid cells, potentially explaining their prolonged immunomodulatory effects.
- Epigenetic reprogramming by MBV offers a mechanism for sustained immune modulation.
- MBV represent a potential therapeutic strategy leveraging biologic scaffold materials for immune system manipulation.
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