Progenitor cells from gene-engineered human induced pluripotent stem cells as synthetic cancer cell alternatives

Introduction Recent studies revealed limitations in genetic stability and recapitulating accurate pathophysiological properties of patient-derived (PD) cancer models opposing challenges for reproducible and translational research. The development of alternative human disease modeling technologies to combat this dilemma might be one strategy to combat this dilemma.

Aims The development of cellular and molecular controlled cancer stem cell alternatives utilizing genetic engineering of human induced pluripotent stem cells (hiPSCs) with transforming elements.

Methods hiPSC culture and differentiation, genetic engineering, various molecular biological assays incl. global OMICS data acquisition and evaluation, in vitro pharmacology, xenotransplantation assay

Results We developed a portfolio of hiPSC with stable overexpression of prominent oncogenes such EGFRvIII, Gli1, TP53R175H, cMYC or IDH1R132H, in a single and double mutation conditions. Thos cells exhibit stable functional properties such as drug resistance levels before and after cryopreservation. Lineage differentiation reveals stable gene alteration in tissue specific progenitor cells. Current studies reveal signs of in vivo tumor formation capacity of those cells, but studies are ongoing. Our medium size drug-screening attempt indicates the potential of our platform technology to serve as a highly biomarker-specific, isogenic controlled assay to identify altered chemotherapy resistance levels of transformed stem cells.

Conclusion Our attempt is a promising approach for alternative human cancer modeling with potential in throughput applications. Maturation of transformed progenitor cells in organoids might help to improve our understanding of the oncogenic potential of selected oncogenes, which might help to develop targeted anti-cancer stem cell therapies.

Publikationsverlauf

Artikel online veröffentlicht:
19. August 2022