ArticlePathology oncology research : POR2026
Beyond animal models: using human pluripotent stem cell-derived stem and progenitor cells to predict cytotoxicity in normal tissues.
Article in Pathology oncology research : POR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Background: The clinical efficacy of anticancer drugs is often limited by dose-dependent toxicity to normal cells, particularly to rapidly dividing stem and progenitor cell populations. Traditional preclinical toxicity screening relies on animal models or primary human cells/immortalized lines, both of which have significant limitations regarding scalability, reproducibility, genetic diversity, and translational relevance. Objective: This study aims to establish and validate a human pluripotent stem cell -based platform for profiling the toxicity of cytostatic drugs on healthy, dividing cell populations, and to compare their sensitivity to that of cancer cell lines. Methods: Two hiPSC lines (male and female) were reprogrammed from umbilical cord blood cells, fully characterized, and differentiated into neural progenitors and mesenchymal derivatives. Dose-response curves were generated using a dilution series of four anticancer drugs and four other pharmacologically active compounds based on cell viability. Toxic half-maximal values (IC Results: The highest sensitivity to DNA-damaging agents was exhibited by pluripotent stem cells, followed by neural progenitors, with mesenchymal derivatives being the least sensitive. Notably, except for mesenchymal cells, both pluripotent stem cells and their differentiated derivatives were more sensitive to cytostatics than cancer cell lines. Conclusion: Human iPSC-derived stem/progenitor cells recapitulate the
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