Tumorigenesis in cells derived from induced pluripotent stem cells

Area of Science:

• Stem Cell Biology
• Regenerative Medicine
• Cancer Biology

Background:

• Induced pluripotent stem (iPS) cells offer promise for cell-replacement therapies.
• A significant risk associated with iPS cell transplantation is teratoma formation from residual undifferentiated cells.
• Distinguishing tumorigenic from nontumorigenic iPS cells is crucial for therapeutic safety.

Purpose of the Study:

• To characterize Nanog-expressing (undifferentiated) iPS cells remaining after differentiation induction.
• To evaluate the tumorigenic potential of Nanog-expressing versus Nanog-negative iPS cell populations.
• To determine if cytological examination can predict teratoma formation risk.

Main Methods:

• Generation of embryoid bodies (EBs) from iPS cells carrying a Nanog–green fluorescent protein (GFP) reporter.
• Inoculation of GFP-positive and GFP-negative EBs into nude mice.
• Cytological examination and morphological analysis (nucleus/cytoplasm ratio) of GFP-positive and GFP-negative cells.

Main Results:

• GFP-positive EB transplantation led to immature teratoma formation (grade 3).
• GFP-negative EB transplantation did not induce tumors.
• GFP-positive cells exhibited a smaller cytoplasmic area and a higher nucleus/cytoplasm ratio compared to GFP-negative cells.

Conclusions:

• Nanog-expressing iPS cells are tumorigenic and pose a risk in cell transplantation.
• Morphological analysis, specifically the nucleus/cytoplasm ratio, can differentiate between tumorigenic and nontumorigenic iPS cells.
• Cytological examination offers a potential method for assessing iPS cell safety prior to transplantation.