Compartmentalized microfluidic culture platform to study mechanism of paclitaxel-induced axonal degeneration.

摘要: Chemotherapy induced peripheral neuropathy is a common and dose-limiting side effect of anticancer drugs. Studies aimed at understanding the underlying mechanism neurotoxicity chemotherapeutic drugs have been hampered by lack suitable culture systems that can differentiate between neuronal cell body, axon or associated glial cells. Here, we developed an in vitro compartmentalized microfluidic system to examine site toxicity To test platform, used paclitaxel, widely drug for breast cancer, because it causes sensory polyneuropathy large proportion patients there no effective treatment. In previous studies, paclitaxel distal axonal degeneration but was unclear if this due direct on consequence body. Using channels allow culturing neurons axons, demonstrate axons are much more susceptible toxic effects paclitaxel. When applied side, clear axons; when soma change length. Furthermore, show recombinant human erythropoietin, which had shown be neuroprotective against neurotoxicity, provides neuroprotection whether body directly. This observation has implications development chemotherapy neuropathies as dorsal root ganglia do not possess blood-nerve-barrier, eliminating one cardinal requirements nervous system. studies degeneration,