Matrix-bound nanovesicles as epigenetic modulators of myeloid cells.

Extracellular vesicles (EV) represent a conserved and highly efficient mechanism for cell-to-cell communication. Matrix-bound nanovesicles (MBV) are a recently identified type of EV embedded within the extracellular matrix with potent local and systemic immunomodulatory effects on myeloid cells. These effects are durable and last beyond the predicted life span of differentiated myeloid cells such as macrophages. The present study investigated MBV-directed epigenetic modification in myeloid precursors as a potential explanation for their prolonged immunomodulatory effects. Flow cytometry and ATAC sequencing studies show that MBV are internalized by myeloid cell progenitors in the bone marrow and in macrophages after terminal differentiation. This internalization is coincident with epigenetic changes that are associated with modulation of macrophage responses to inflammatory stimuli. Furthermore, MBV treatment differentially alters chromatin accessibility as a function of cell differentiation state (i.e., myeloid progenitor versus macrophage). The present study shows the epigenetic effects of MBV on myeloid cells, representing a potential avenue to exploit the therapeutic potential of biologic scaffold materials.