Human ES and iPS Cells Display Less Drug Resistance Than Differentiated Cells, and Naïve-State Induction Further Decreases Drug Resistance

Abstract

Pluripotent stem cells (PSCs) possess unique characteristics that distinguish them from other cell types. Among them, human embryonic stem (ES) cells are gaining attention as a powerful tool for human toxicity assessment without the use of experimental animals, and the embryonic stem cell test (EST) was introduced for this purpose. However, some human PSCs, particularly induced pluripotent stem (iPS) cells, have not been thoroughly investigated and compared with other cell types or cell states in terms of chemical sensitivity. Aiming to close this gap, we assessed and compared several human PSC lines for their reaction to chemical exposure. We report that iPS cells are more sensitive to chemical exposure than other cell types, including ES cells. Specifically, RIKEN-2A human iPS cells were 1.5 times on average more sensitive to chemical exposure than KhES-3 human ES cells, and both were several times more sensitive to chemical exposure than non-pluripotent cell types. In addition, we showed that iPS cells subjected to naïve-state induction procedures exhibited a sharp increase in chemical sensitivity. However, upon passage of these naïve-like cells in conventional PSC culture medium, their sensitivity to chemical exposure decreased. In conclusion, we revealed differences in sensitivity to chemical exposure among different types and states of PSCs and that naïve-state induction could increase this sensitivity.