Transmission electron microscopy images of bone nodules formed in osteogenically induced MSCs (A–D) and iPSCs (E–H) cultures. Cells are indicated as “C” in the panels. (A) Cross-section through the MSCs on day 10. Calcium phosphate-containing vesicles (black spot areas) were visible around the cells and in the extracellular spaces, which contained fibrous ECM (asterisks). Scale bar: 5 μm. (B) Magnified image of the square in (A). Micrograph showing mineral aggregates (asterisk) immediately outside the cell. Scale bar: 100 nm. Inset: the selected area electron diffraction (SAED) pattern of the mineral aggregate was similar to that of hydroxyapatite. (C) Micrograph of a cross-section through the MSCs on day 30. Electron-dense vesicles (dense black spots) were evident immediately outside cells (arrowheads), within membrane invaginations (black arrow), and within cells (white arrow). Fibrous ECM was visible (asterisks). Scale bar: 5 μm. (D) Magnified image of the dotted square in (C). Micrograph showing dense mineral (asterisk) immediately outside the cell membrane. Scale bar: 500 nm. Inset: SAED analysis of the dense areas was indicative of hydroxyapatite. (E) Cross-section through the iPSCs on day 10. An electron-sparse structure (asterisks) surrounded the cells. Scale bar: 2 μm. (F) Magnified image of the square in (E). Electron-dense needle-like minerals are scattered (asterisk). Scale bar: 50 nm. Inset: SAED analysis of the scattered mineral structure indicated a lack of a textured crystalline diffraction pattern, which suggests that the structure is relatively amorphous and that mineralization has been initiated. (G) Cross-section through the bone nodule portion of iPSCs on day 30. Heavily electron-dense vesicles (asterisks) were evident in the ECM spaces. A vesicle, which appeared to be dispersing its mineral contents (arrowheads), was also visible. Fibrous structures were not evident in the extracellular spaces. Scale bar: 5 μm. (H) Magnification of the dotted square in (G). The SAED pattern of an electron-dense vesicle (asterisk) was identical to that of typical hydroxyapatite (inset). Scale bar: 500 nm.