Journal Article

DZNE-2021-00442

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Modeling chemotherapy induced neurotoxicity with human induced pluripotent stem cell (iPSC)-derived sensory neurons.

Schinke, C. ; Fernandez Vallone, V. ; Ivanov, A. ; Peng, Y. ; Körtvelyessy, P.DZNE* ; Nolte, L. ; Huehnchen, P. ; Beule, D. ; Stachelscheid, H. ; Boehmerle, W. ; Endres, M. (Last author)DZNE*

2021
Academic Press Orlando, Fla.

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Please use a persistent id in citations: doi:10.1016/j.nbd.2021.105391

Abstract: 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. We therefore aimed to evaluate whether sensory neurons derived from induced pluripotent stem cells (iPSC-DSN) can serve as human disease model system for CIPN. Treatment of iPSC-DSN for 24 h with the neurotoxic drugs paclitaxel, bortezomib, vincristine and cisplatin led to axonal blebbing and a dose dependent decline of cell viability in clinically relevant IC50 ranges, which was not observed for the non-neurotoxic compounds doxorubicin and 5-fluorouracil. Paclitaxel treatment effects were less pronounced after 24 h but prominent when treatment was applied for 72 h. Global transcriptome analyses performed at 24 h, i.e. before paclitaxel-induced cell death occurred, revealed the differential expression of genes of neuronal injury, cellular stress response, and sterol pathways. We further evaluated if known neuroprotective strategies can be reproduced in iPSC-DSN and observed protective effects of lithium replicating findings from rodent dorsal root ganglia cells. Comparing sensory neurons derived from two different healthy donors, we 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.

Keyword(s): Antineoplastic Agents: toxicity (MeSH) ; Axons: drug effects (MeSH) ; Axons: pathology (MeSH) ; Cell Line (MeSH) ; Cell Survival: drug effects (MeSH) ; Cell Survival: physiology (MeSH) ; Dose-Response Relationship, Drug (MeSH) ; Humans (MeSH) ; Induced Pluripotent Stem Cells: drug effects (MeSH) ; Induced Pluripotent Stem Cells: pathology (MeSH) ; Sensory Receptor Cells: drug effects (MeSH) ; Sensory Receptor Cells: pathology (MeSH) ; Time-Lapse Imaging: methods (MeSH) ; 3R ; Chemotherapy induced neuropathy ; Induced pluripotent stem cell derived sensory neurons (iPSC-DSN) ; Lithium ; Replacement ; Transcriptome

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Contributing Institute(s):

1. Interdisciplinary Dementia Research (AG Endres)
2. Clinical Neurophysiology and Memory (AG Düzel)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

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Database coverage:
; ; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article Schinke, C. ; Fernandez Vallone, V. ; Ivanov, A. ; Peng, Y. ; Körtvelyessy, P.DZNE* ; Nolte, L. ; Huehnchen, P. ; Beule, D. ; Stachelscheid, H. ; Boehmerle, W. ; Endres, M. (Last author)DZNE*
Dataset for: Modeling chemotherapy induced neurotoxicity with human induced pluripotent stem cell (iPSC)-derived sensory neurons.
Data in Brief 38, 107320 (2021) [10.1016/j.dib.2021.107320]2021   Files  Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

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