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

Area of Science:

• Neuroscience
• Stem Cell Biology
• Pharmacology

Background:

• Peripheral neuropathy (PN) is a common chemotherapy side effect, impairing quality of life.
• Understanding PN pathophysiology is limited by the scarcity of human sensory neurons (SNs).
• Previous methods yielded limited SNs from rare blood sources.

Purpose of the Study:

• To develop a scalable method for generating human SNs from adult peripheral blood (PB).
• To establish a high-content screening platform for studying chemotherapy effects on neurons.
• To identify potential therapeutic targets and drugs for chemotherapy-induced PN.

Main Methods:

• Developed a protocol to convert adult PB into induced sensory neurons (iSNs) via neural precursor differentiation.
• Utilized cryogenically preserved adult PB without mobilization drugs.
• Adapted iSNs for high-throughput, high-content screening assays, including neurite morphology analysis.

Main Results:

• Successfully generated human iSNs from conventionally drawn adult PB.
• Demonstrated the utility of iSNs in a high-content screening platform.
• Showcased the ability to detect chemotherapy-induced alterations in neurite morphology.

Conclusions:

• This study presents the first platform using adult PB-derived iSNs for studying peripheral nervous system neuropathies.
• The platform enables target and drug screening for preventing, blocking, or repairing chemotherapy-induced PN.
• This approach overcomes limitations of previous SN generation methods, offering a scalable solution.