Progenitor cells derived from gene‐engineered human induced pluripotent stem cells as synthetic cancer cell alternatives for in vitro pharmacology

Autor: Constanze Uhlmann, Ann‐Christin Nickel, Daniel Picard, Andrea Rossi, Guanzhang Li, Barbara Hildebrandt, Gabriele Brockerhoff, Farina Bendt, Ulrike Hübenthal, Michael Hewera, Hans‐Jakob Steiger, Dagmar Wieczorek, Aristoteles Perrakis, Wei Zhang, Marc Remke, Katharina Koch, Julia Tigges, Roland S. Croner, Ellen Fritsche, Ulf D. Kahlert
Rok vydání: 2022
Předmět:
Zdroj: Biotechnology Journal. 17:2100693
ISSN: 1860-7314
1860-6768
DOI: 10.1002/biot.202100693
Popis: Limitations in genetic stability and recapitulating accurate physiological disease properties challenge the utility of patient-derived (PD) cancer models for reproducible and translational research. A portfolio of isogenic human induced pluripotent stem cells (hiPSCs) with different pan-cancer relevant oncoprotein signatures followed by differentiation into lineage-committed progenitor cells was genetically engineered. Characterization on molecular and biological level validated successful stable genetic alterations in pluripotency state as well as upon differentiation to prove the functionality of our approach. Meanwhile proposing core molecular networks possibly involved in early dysregulation of stem cell homeostasis, the application of our cell systems in comparative substance testing indicates the potential for cancer research such as identification of augmented therapy resistance of stem cells in response to activation of distinct oncogenic signatures.
Databáze: OpenAIRE
načítá se...