In vitro assessment of chemotherapy-induced neuronal toxicity

Snyder, Chelsea; Yu, Lanlan; Ngo, Tin; Sheinson, Daniel; Zhu, Yuda; Tseng, Min; Misner, Dinah; Staflin, Karin

doi:10.1016/j.tiv.2018.02.004

Cited by 19 publications

(20 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since multiple chemotherapeutic drugs cause sensory peripheral neuropathy, the effect of additional agents on neurite complexity was assessed. Concentrations of each drug needed for robust quantification of changes in neurite area were selected based on published data 13,19 and treatment was restricted to 72 hr based on the data from paclitaxel presented above.…”

Section: Differential Sensitivity Of Ipsc-sns To Chemotherapeutic Drugsmentioning

confidence: 99%

“…In recent years, human induced pluripotent stem cell (iPSC)-derived neurons have been used for the study of CIPN. Commercially available iPSC-derived neurons (e.g., iCell Neurons ® and Peri.4U Neurons ® ) have been evaluated as a model of neurotoxicity 9 , used to screen for neurotoxic compounds [10][11][12][13] , and utilized for functional validation of genes identified in human genome wide association studies of CIPN 9, [14][15][16] . The use of human iPSC-derived neurons affords an advantage over rodent DRG neurons in their human origin and the potential to differentiate into specific peripheral sensory neuron populations.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel

Xiong

Chua

Stage

et al. 2020

Preprint

View full text Add to dashboard Cite

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse event associated with treatment with paclitaxel and other chemotherapeutic agents. The prevention and treatment of CIPN are limited by a lack of understanding of the molecular mechanisms underlying this toxicity. In the current study, a human induced pluripotent stem cell-derived sensory neuron (iPSC-SN) model was developed for the study of chemotherapy-induced neurotoxicity. The iPSC-SNs express proteins characteristic of nociceptor, mechanoreceptor and proprioceptor sensory neurons and show Ca 2+ influx in response to capsaicin, ,-meATP and glutamate. iPSC-SNs are relatively resistant to the cytotoxic effects of paclitaxel, with IC 50 values of 38.1 M (95% CI: 22.9 -70.9 M) for 48 hr exposure and 9.3 M (95% CI: 5.7 -16.5 M) for 72 hr treatment. Paclitaxel causes dose-and time-dependent changes in neurite network complexity detected by III-tubulin staining and high content imaging. The IC 50 for paclitaxel reduction of neurite area was 1.4 M (95% CI: 0.3 -16.9 M) for 48 hr exposure and 0.6 M (95% CI: 0.09 -9.9 M) for 72 hr exposure. Decreased mitochondrial membrane potential, slower movement of mitochondria down the neurites and changes in glutamate-induced neuronal excitability were also observed with paclitaxel exposure. The iPSC-SNs were also sensitive to docetaxel, vincristine and bortezomib.Collectively, these data support the use of iPSC-SNs for detailed mechanistic investigations of genes and pathways implicated in chemotherapy-induced neurotoxicity and the identification of novel therapeutic approaches for its prevention and treatment.

show abstract

Section: Differential Sensitivity Of Ipsc-sns To Chemotherapeutic Drugsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel

Xiong

Chua

Stage

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Despite some disadvantages, such as the high cost of iPSC generation and a time and labor intensive protocol for neuronal differentiation, human iPSC-derived neurons play an important role in disease modeling and are used to study neurotoxicity of environmental contaminants 50 or chemotherapeutic drugs [51][52][53] . Limiting the utility of iPSCs generated from disease-mutation carriers is the lack of isogenic unaffected controls.…”

Section: Discussionmentioning

confidence: 99%

Heavy metals contaminating the environment of a progressive supranuclear palsy cluster induce tau accumulation and cell death in cultured neurons

Alquézar

Felix

McCandlish

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The development of in vivo and in vitro models has provided valuable tools for studying the pathogenesis of CIPN and intervention strategies. 28,29,40,78,79…”

Section: Pathophysiology Of Cipnmentioning

confidence: 99%

A Comparative Review of Chemotherapy-Induced Peripheral Neuropathy in In Vivo and In Vitro Models

2019

View full text Add to dashboard Cite

Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect caused by several classes of widely used anticancer therapeutics. Chemotherapy-induced peripheral neuropathy frequently leads to dose reduction or discontinuation of chemotherapy regimens, and CIPN symptoms can persist long after completion of chemotherapy and severely diminish the quality of life of patients. Differences in the clinical presentation of CIPN by widely diverse classifications of anticancer agents have spawned multiple mechanistic hypotheses that seek to explain the pathogenesis of CIPN. Despite its clinical relevance, common occurrence, and extensive investigation, the pathophysiology of CIPN remains unclear. Furthermore, there is no unequivocal gold standard for the prevention and treatment of CIPN. Herein, we review in vivo and in vitro models of CIPN with a focus on histopathological changes and morphological features aimed at understanding the pathophysiology of CIPN and identify gaps requiring deeper exploration. An elucidation of the underlying mechanisms of CIPN is imperative to identify potential targets and approaches for prevention and treatment.

show abstract

In vitro assessment of chemotherapy-induced neuronal toxicity

Cited by 19 publications

References 67 publications

Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel

Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel

Heavy metals contaminating the environment of a progressive supranuclear palsy cluster induce tau accumulation and cell death in cultured neurons

A Comparative Review of Chemotherapy-Induced Peripheral Neuropathy in In Vivo and In Vitro Models

Contact Info

Product

Resources

About