Research Article

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

Table 1

Main histological findings and immunohistochemistry profile in the tumors generated.

Cell originClonemyc during reprogrammingTeratomaMalignant GCTImmunohistochemistry
EctodermMesodermEndodermECYSTMYCSALL4OCT4CD30PLAPGPC3AFP

Human ESCES 5NoNE rosettes, pigmented epitheliumCartilageGlandsNDNDNDNDNDNDND
Human ESCS053NoNE rosettes, pigmented epitheliumCartilageGlands<5% EC-like30% EC-like 1+EC-like 3+
10% TE 1+
Neg.Neg.Neg.NDND
Human hepatocytesOKS1NoNerves, rare NE rosettesBone, adipose tissueGlands, 10% liver10%60% EC 1+EC 3+
10% TE 3+
EC 3+EC 1+Neg.20% EC 1+
30% TE 3+
Fetal hepatocytes 2+
Human hepatocytesOKSM11Yes100%Diffuse 2+Diffuse 3+90% 3+90% 3+90% 2+/3+5% 3+Neg.
Human hepatocytesOKSM12YesMinute foci immature mesenchyme95%5%Diffuse 1+/2+Diffuse 3+90% 3+90% 2+/3+70% 2+/3+YST 3+YST 3+
Human hepatocytesOKSM2Yes100%Diffuse 3+Diffuse 3+Diffuse 3+30% 2+60% 2+2+ 10%Neg.
Human hepatocytesOKSM5YesNE rosettes, pigmented epitheliumBone, cartilageGlands 10%5%EC 3+EC & YST 3+
10% TE 2+
EC 3+ EC 2+/3+EC 3+YST 3+YST 3+
Human hepatocytesIH1-1YesFoci immature mesenchyme~100%NDNDNDNDNDNDND
Human hepatocytesIH5-1BYesRare NE rosettes, pigmented epitheliumBone, cartilageGlands40%–60%EC 2+/3+EC 3+EC 2+70% EC 2+90% EC 2+/3+20% EC 1+ 5% TE 2+Neg.
Human fibroblastsiFS21YesVery rare NE rosettesSmooth muscleGlandsNDNDNDNDNDNDND
Human fibroblastsiFS22YesVery rare NE rosettes, immature neurogliaSmooth muscleDigestive tract segmentsNDNDNDNDNDNDND
Human fibroblastsICCLYesNE rosettes, neurogliaSmooth muscle, cartilageGlandsNDNDNDNDNDNDND
Human CD34+ cellsiPS 2NoNE rosettes, neurogliaCartilageGlandsNDNDNDNDNDNDND
Human CD34+ cellsiPS 6NoRare NE rosettesMinute foci immature mesenchyme>90%5%EC 1+/2+EC & YST 3+ EC 3+40% EC 1+20% EC 2+YST 3+ YST 3+
Human CD34+ cellsiPS 43NoNE rosettesMesenchymal cellsGlandsNDNDNDNDNDNDND
Mouse hepatocyteshep1 p10Stably integratedNeurogliaSmooth musclePancreas, glands, squamous epithelium5%NDNDNDNDNDNDND
Mouse hepatocyteshep2 p10Stably integratedNeurogliaSmooth muscle, cartilageGlands, squamous epithelium5–10%NDNDNDNDNDNDND
Mouse hepatocyteshep3 p8Stably integratedNeurogliaSmooth muscleGlands, squamous epithelium5%10% EC 1+
1% EC 2+
EC 2+/3+30% EC 2+NCRNCRNeg.NCR
Mouse HSChem1 p11Stably integratedNeurogliaStriated & smooth muscle, cartilage, adipose tissuePancreas, glands, squamous epithelium5–10%NDNDNDNDNDNDND
Mouse HSChem2 p11Stably integratedNeuroglia, pigmented epitheliumStriated & smooth muscle, cartilage, adipose tissuePancreas, glands, squamous epithelium5–10%NDNDNDNDNDNDND
Mouse HSChem3 p10Stably integratedNeuroglia, pigmented epitheliumStriated & smooth muscle, cartilagePancreas, liver, glands, squamous epithelium5–10%10% EC 1+EC 3+
5% TE 1+/2+
30% EC 2+NCRNCRStriated muscle 1+NCR

EC = embryonal carcinoma.
YST = yolk sac tumor.
ND = not done.
NCR = no expected antibody cross-reaction with murine tissues.
HSC = hematopoietic stem cells.