Transplanted DPPIV-positive hepatocytes convert into BECs through a ductal plate configuration in acute hepato-biliary injury.

<p>Shown are serial liver sections stained histochemically for DPPIV, GGT, and with double immunofluorescence for DPPIV with laminin, hepatocyte marker (C/EBP-α), BEC markers (CK-19, CK-7, HNF-1β), for CK-19/CPS1 (hepatocyte-specific enzyme), and HNF-1β/HNF-4α (hepatocyte-specific marker). (A1–A6) At one week, periportally entrapped DPPIV-positive cells can be traced in 4–5 sequential sections, are surrounded by laminin, and express only hepatocyte markers (arrows). (B1–B12) At two weeks, the linearly arranged DPPIV-positive cells along the portal veins can be tracked at least in 20 successive sections and are a bilayered structure, indicating that they form a two-layered plate of cells. The plate of DPPIV-positive cells is surrounded by laminin and comprises cells with characteristics of hepatocytes (big arrows), BECs (arrows), and both. A lineage relationship is suggested between these DPPIV-positive cells in the plate, with CPS1(+)/CK-19(-) in some section levels (B4–B6) and CPS1(-), CEBP-α(-)/CK-19(+), CK-7(+), HNF-1β(+) in sequential levels of sections (B7–B12). In some sections, DPPIV-positive plate expressing BEC markers is in contiguity to DPPIV-positive hepatocyte clusters (B10, B11). (C1–C9) At four weeks, most cells of DPPIV-positive plates (arrows) express BEC markers, CK-19(+), CK-7(+), and HNF-1β(+). Lumens are detected focally between the two-layered plates. Serial sections reveal the formation of lumens being along the longitudinal axis of portal veins. (D) Schematic representation of the stepwise conversion of transplanted hepatocytes into BECs. (Original magnification: 200x) Scale bars: 100 μm.