2020
DOI: 10.1111/cts.12912
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Abstract: 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,… Show more

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Cited by 28 publications
(30 citation statements)
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“…The significant impact of TIPN on cancer patients' quality of life has mobilized many efforts to improve understanding of the mechanism underlying this toxicity. Diverse approaches have been utilized to identify the direct effects of paclitaxel in vivo with rodent behavioral studies [38,39], and in vitro with procured postmortem human dorsal root ganglion tissue [40,41] and human-derived neurons reprogrammed from iPSCs [42][43][44][45][46], providing a framework to identify general phenotypic features of disease. A major advantage to the use of iPSC-derived neurons is the ability to conduct studies with consideration to a patient's unique genetic diversity.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…The significant impact of TIPN on cancer patients' quality of life has mobilized many efforts to improve understanding of the mechanism underlying this toxicity. Diverse approaches have been utilized to identify the direct effects of paclitaxel in vivo with rodent behavioral studies [38,39], and in vitro with procured postmortem human dorsal root ganglion tissue [40,41] and human-derived neurons reprogrammed from iPSCs [42][43][44][45][46], providing a framework to identify general phenotypic features of disease. A major advantage to the use of iPSC-derived neurons is the ability to conduct studies with consideration to a patient's unique genetic diversity.…”
Section: Discussionmentioning
confidence: 99%
“…On the other hand, our study found that paclitaxel decreased sodium currents recorded in the cell soma and si SBF2 prevented this inhibition. Axon degeneration and alteration in sodium channels are two major mechanisms of paclitaxel-induced TIPN [ 46 ]. However, how these two mechanisms interact is still not clear.…”
Section: Discussionmentioning
confidence: 99%
“…This approach represents a model of traumatic nerve injury and allows for nerve injury and regeneration processes to be studied. Other studies have used neurotoxins to induce nerve injury, for example, chemotherapeutic agents ( Jones et al, 2018 , Xiong et al, 2020 ). Critical to the value of these experiments is representative dosing regimen.…”
Section: What Should Sc-sns Be Used For?mentioning
confidence: 99%
“…However, Ncardia discontinued its commercial Peri4U™ product and instead offers a custom-ordered hiPSC-peripheral neuronal cell model that is not readily available. Some commercial vendors offer undifferentiated neural crest cells, but these cells require extensive expertise to maintain reproducibility and readily available cultures [93]. Furthermore, differences in seeding conditions, pluripotency status of hiPSCs prior to differentiation, and in the differentiation and maturation protocol can significantly alter the composition of the desired cell model [93].…”
Section: In Vitro Modelsmentioning
confidence: 99%
“…Some commercial vendors offer undifferentiated neural crest cells, but these cells require extensive expertise to maintain reproducibility and readily available cultures [93]. Furthermore, differences in seeding conditions, pluripotency status of hiPSCs prior to differentiation, and in the differentiation and maturation protocol can significantly alter the composition of the desired cell model [93]. Additionally, lack of in-depth phenotypic and functional characterization is a common drawback of all hiPSC-peripheral neuronal products currently available in the commercial market.…”
Section: In Vitro Modelsmentioning
confidence: 99%