ePoster

Modelling chemotherapy-induced peripheral neuropathy on-a-chip

Xandor Spijkers, Georgia Avramidou, Wouter Strijker, Mary McFarlane, Catherine Rodger, Jay Harper, Luke Masterson, Nienke Wevers
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Xandor Spijkers, Georgia Avramidou, Wouter Strijker, Mary McFarlane, Catherine Rodger, Jay Harper, Luke Masterson, Nienke Wevers

Abstract

Peripheral neuropathy is characterized by damage to the peripheral nerves, leading to symptoms such as numbness, tingling, and pain in the extremities. While peripheral neuropathy can be caused by several factors, a common cause is toxicity from chemotherapeutic drugs.We studied chemotherapy-induced peripheral neuropathy (CIPN) using the OrganoPlate, a microfluidic cell culture platform that allows culture of 40 chips in parallel. Human iPSC-derived peripheral neurons were embedded in extracellular matrix gel and seeded into the OrganoPlate, after which they extended their axons into an adjacent layer of gel. Chips were then exposed to chemotherapeutic drugs known to induce peripheral neuropathy in the clinic, at different concentrations (0.1-1-10-100 nM) and for different durations (48-72-96 hours). The compounds’ effects on axonal outgrowth were assessed by fluorescent cell labeling and confocal imaging.All tested compounds induced axonal damage in a dose-dependent and time-dependent manner. Vincristine and monomethyl auristatin E (MMAE) exhibited the highest level of damage, followed by vinblastine, combretastatin, and hemiasterlin. The assay shows high reproducibility, evidenced by a Z-factor of 0.746 for 96-hour exposures.The high reproducibility of our assay, along with the platform's high-throughput nature and compatibility with automation, holds great potential for drug screening focused on axonal toxicity in the context of peripheral neuropathy.

Unique ID: fens-24/modelling-chemotherapy-induced-peripheral-935aa504