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

Figure 3

iPSC generated from human hepatocytes, using the OKS integrative vector. The tumors produced were in part cystic (a, H&E 20x) and showed features of immature teratoma. Fibrous bone was part of the mesodermal derivatives and was surrounded by loosely arranged mesenchymal cells (b, H&E 200x). Endoderm-derived structures consisted of variably immature glands focally in close relationship to fetal-like hepatocytes (arrow) (c, H&E 200x). Rarely, confluent atypical glandular structures showed stratification (d, H&E 100x); stratified glands (arrow) were also focally close to nests of fetal-like hepatocytes (arrowhead) (e, H&E 400x). Upon immunohistochemical evaluation, the atypical glands displayed strong expression of SALL4, a feature shared by some of the teratoma components of which the hepatocyte plates are (arrowheads) (f, 200x). Strong reactivity to OCT4 was also seen (g, 200x). MYC reactivity was only mild (h, 200x). The fetal-appearing hepatocytes expressed AFP (i, 200x) and albumin (j, in situ hybridization, 200x).

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