A personalised human iPSC model for chemotherapy-induced neurotoxicity
2021
Charité - Universitätsmedizin Berlin, Berlin, Germany
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent, potentially irreversible adverse effect of cytotoxic chemotherapy often leading to a reduction or discontinuation of treatment which negatively impacts patients' prognosis. To date, however, neither predictive biomarkers nor preventive treatments for CIPN are available, which is partially due to a lack of suitable experimental models. The authors, therefore, aimed to evaluate whether sensory neurons derived from induced pluripotent stem cells (iPSC-DSN) can serve as a human disease model system for CIPN. Treatment of iPSC-DSN with four neurotoxic drugs led to axonal blebbing and a dose-dependent decline of cell viability in clinically relevant ranges, which was not observed for non-neurotoxic compounds. Comparing sensory neurons derived from two different healthy donors, the authors found preliminary evidence that these cell lines react differentially to neurotoxic drugs as expected from the variable presentation of CIPN in patients. In conclusion, iPSC-DSN are a promising platform to study the pathogenesis of CIPN and to evaluate neuroprotective treatment strategies. In the future, the application of patient-specific iPSC-DSN could open new avenues for personalized medicine with individual risk prediction, choice of chemotherapeutic compounds and preventive treatments.
Modeling chemotherapy induced neurotoxicity with human induced pluripotent stem cell (iPSC) -derived sensory neurons
Wolfgang Boehmerle
Added on: 10-21-2021
[1] https://www.sciencedirect.com/science/article/pii/S0969996121001406
