Unraveling chemotherapy‐induced peripheral neuropathy: In vitro and in vivo models of sensory nerve dysfunction

Large, Danielle

doi:10.1002/jnr.24323

Cited by 1 publication

(1 citation statement)

References 19 publications

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“…To date, the cellular pathophysiology of the disease has predominately been investigated using rodent cellular models. However, reported limitations of these models and biological differences between rodent and human physiology limit translatability between the species and the fundamental pathways of chemotherapy‐induced PN remain unknown. Thus, large‐scale generation of human sensory neurons (SNs) is an imperative to engineer therapeutics that target and attenuate chemotherapy‐induced PN condition.…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy-Induced Neuropathy and Drug Discovery Platform Using Human Sensory Neurons Converted Directly from Adult Peripheral Blood

Vojnits

Mahammad

Collins

et al. 2019

Stem Cells Translational Medicine

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Chemotherapy‐induced peripheral neuropathy (PN) is a disorder damaging the peripheral nervous system (PNS) and represents one of the most common side effects of chemotherapy, negatively impacting the quality of life of patients to the extent of withdrawing life‐saving chemotherapy dose or duration. Unfortunately, the pathophysiological effects of PN are poorly understood, in part due to the lack of availability of large numbers of human sensory neurons (SNs) for study. Previous reports have demonstrated that human SNs can be directly converted from primitive CD34+ hematopoietic cells, but was limited to a small‐scale product of SNs and derived exclusively from less abundant allogenic sources of cord or drug mobilized peripheral blood (PB). To address this shortcoming, we have developed and report detailed procedures toward the generation of human SN directly converted from conventionally drawn PB of adults that can be used in a high‐content screening platform for discovery‐based studies of chemotherapy agents on neuronal biology. In the absence of mobilization drugs, cryogenically preserved adult human PB could be induced to (i)SN via development through expandable neural precursor differentiation. iSNs could be transferable to high‐throughput procedures suitable for high‐content screening applicable to neuropathy for example, alterations in neurite morphology in response to chemotherapeutics. Our study provides the first reported platform using adult PB‐derived iSNs to study peripheral nervous system‐related neuropathies as well as target and drug screening potential for the ability to prevent, block, or repair chemotherapy‐induced PN damage. stem cells translational medicine 2019;8:1180–1191

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Section: Introductionmentioning

confidence: 99%