Histological analysis of 3D FTSEC spheroids. (a) Three dimensional spheroid cultures stained by hematoxylin and eosin. At (i) 15 days, the core of the spheroids contains abundant matrix material (*), covered by an epithelial cell monolayer (arrow) or cellular cap structure (arrowhead). (ii) After 40 days no viable cells remain within the core of the spheroids. A viable monolayer covers the surface of the spheroid (arrow), degenerate nuclear debris can be seen within the matrix core (arrowhead). (b) Electron microscopy of FTSEC spheroids. Features of epithelial cells in vivo are detected in 3D cultured FTSECs including (i) microvilli and cell-cell junction complexes including (ii,iii) tight junctions (white arrows and inset) and (iv) adherens junctions (white arrows and inset). Electron microscopy.