Fig. 2

Transmission electron micrography of regulated cell death (RCD) in human macrophages and cell-to-cell interactions with human bone marrow mesenchymal stem cells. A human macrophage exposed to metallic nanoparticles undergoing (top left) pyroptosis, with an intact nucleus and disrupted plasma membrane, and (bottom left) apoptosis, featuring an intact plasma membrane and formation of membrane blebs. Right, co-culture of macrophages and MSCs in the presence of metallic nanoparticles. Shows human monocyte-derived macrophages (phorbol-12-myristate-13-acetate–activated THP-1 cells) in close contact with mesenchymal stem/stromal cells (MSCs). MSCs appear as large cells with clear cytoplasm, morphologically distinguishable from macrophages. The orange arrow indicates a tight membrane contact between an MSC and a macrophage, and the red arrow the presence of extracellular vesicles (~ 100–200 nm in size) near the cell-to-cell contact. Mitochondria in both cells appear co-localized to the side of the cell-to-cell contact. Macrophage to MSC ratio is 2:1. Left, original magnification × 3000. Right, × 2000 of macrophage to MSC co-culture 12 h after pyroptosis induction in macrophages; scale bars are 5 μm (top left), 2 μm (bottom left), 5 μm (right). One original representative image in 3 is shown (Naji Lab). Cyto, cytoplasm; N, nucleus; M, mitochondria; MΦ, macrophage; MSC, mesenchymal stem/stromal cell