Human Hepatocyte-Derived Induced Pluripotent Stem Cells: MYC Expression, Similarities to Human Germ Cell Tumors, and Safety Issues

Figure 7

iPSC generated from mouse hepatocytes. All iPSC with mouse hepatic origin produced solid mixed germ cell tumors (a, H&E 20x). The teratoma components showed derivatives from all three germ layers, with development among other endodermal structures of ducts and pancreas (arrow) (b, H&E 200x), of cartilage as mesodermal derivative (star) (c, H&E 200x) and neuroglial tissue as ectodermal derivative (arrow) (c). Fetal-type hepatocyte plates were focally radially arranged around a centrilobular-like vein (arrowhead) (d, H&E 200x). A minor embryonal carcinoma component was composed of tumor cells arranged in cords and gland-like structures and forming small dispersed nests (star) within the neuroglial component (arrow); ganglion-like cells (arrowheads) are also seen (e, H&E 200x). Strong nuclear reactivity to SALL4 (f, 200x) and OCT4 (g, 200x) was seen in the embryonal carcinoma cells. MYC nuclear reactivity was faint and focal in the embryonal carcinoma component and moderate only in less than 1% of the cells (arrowheads); a minority of the neuroglial cells (arrow) also showed very faint nuclear staining (h, 200x).

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