We also observed that sEVs either from normal control or cholesteatoma patients increased keratinocyte proliferation higher than co-incubation with pure HMGB1 protein and that the increase of keratinocyte proliferation by sEVs was efficiently blocked by the blocking antibody indicating a HMGB1-mediated effect (Figure 4A–C). Here, HMGB1 is linked to cholesteatoma.