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

Figure 4

iPSC generated from human hepatocytes, using the OKSM integrative vector. The generated tumors were mostly solid, with an intimately admixed minor component of irregular gland-like spaces (arrow); tumor cells formed serpiginous ribbons around central foci of tumor necrosis (star) (a, H&E 20x). Rarely, minute foci of immature mesenchymal cells were seen (arrow) (b). The major component was composed of pleomorphic malignant-appearing embryonal carcinoma cells that were large and primitive-appearing, with vesicular nuclei and prominent nucleoli; mitoses (arrow) and apoptotic bodies (arrowheads) were numerous (b, inset, H&E 400x). Gland-like spaces lined by immature cells were focally seen and corresponded to a minor yolk sac tumor component (arrows) (c, H&E 100x). Intravascular tumor embolism from the embryonal carcinoma component, a further malignancy criterion, was seen (d, H&E 200x). In the embryonal carcinoma component, strong and diffuse nuclear expression of SALL4 (e, 200x) and OCT4 (f, 200x) was seen, as well as moderate-to-strong membranous and cytoplasmic PLAP (g, 200x), and CD30 (h, 200x) reactivity. Contrariwise, the yolk sac component showed strong GPC3 (i, 200x) and AFP (j, 200x) reactivity. Pooled cytokeratins were expressed in both components but strongly in the yolk sac glandular structures compared to in the embryonal carcinoma component (k, 200x). MYC nuclear reactivity was seen exclusively in the embryonal carcinoma cells (l, 200x).

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