Characterization of human iPSC-derived sensory neurons and their functional assessment using multi electrode array

Area of Science:

• Neuroscience
• Stem Cell Biology
• Pharmacology

Background:

• Dorsal root ganglia (DRG) sensory neurons are crucial for pain signaling but are difficult to culture and yield low numbers from animal models.
• Existing animal-derived models present challenges with interspecies differences and supply stability for in vitro studies.
• Human induced pluripotent stem cell (hiPSC)-derived sensory neurons present a potential solution to these limitations.

Purpose of the Study:

• To characterize hiPSC-derived sensory neurons as a viable in vitro model for nociceptive research.
• To investigate the functional properties, gene/protein expression, and drug responses of these hiPSC-derived neurons.
• To evaluate their utility in drug discovery for pain-related conditions.

Main Methods:

• Cultured and characterized hiPSC-derived sensory neurons.
• Investigated expression of sensory neuron-related genes and proteins.
• Utilized Multi-Electrode Array (MEA) to analyze neuronal activity and drug responses.

Main Results:

• hiPSC-derived sensory neurons expressed key nociceptor, mechanoreceptor, and proprioceptor markers, forming a heterogeneous population.
• Neurons responded to both noxious and non-noxious stimuli, demonstrating functional relevance.
• Specific drug inhibitors (histamine inhibitors, ProTx-II, Nav1.7 inhibitor) modulated neuronal excitability and spontaneous activity differently.

Conclusions:

• hiPSC-derived sensory neurons successfully replicate key characteristics of primary sensory neurons.
• These cells provide a stable and scalable in vitro model, overcoming limitations of animal-derived DRG.
• The combination of hiPSC-derived sensory neurons and MEA is a promising platform for preclinical drug discovery in pain research.