2. Academic Validation
  3. Profiling human iPSC-derived sensory neurons for analgesic drug screening using a multi-electrode array

Profiling human iPSC-derived sensory neurons for analgesic drug screening using a multi-electrode array

  • Cell Rep Methods. 2025 May 19;5(5):101051. doi: 10.1016/j.crmeth.2025.101051.
Christian Kuete Fofie 1,  Rafael Granja-Vazquez 1,  Vincent Truong 2,  Patrick Walsh 2,  Theodore Price 1,  Swati Biswas 3,  Gregory Dussor 1,  Joseph Pancrazio 4,  Benedict Kolber 5
Affiliations

Affiliations

  • 1 Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA.
  • 2 Anatomic Incorporated, Minneapolis, MN 55413, USA.
  • 3 Department of Mathematical Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.
  • 4 Department of Bioengineering, The University of Texas at Dallas, Richardson, TX 75080, USA.
  • 5 Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA. Electronic address: benedict.kolber@utdallas.edu.
PMID: 40367946 DOI: 10.1016/j.crmeth.2025.101051
Abstract

Chronic pain is a global health issue, yet effective treatments remain limited due to poor preclinical-to-human translation. To address this, we developed a high-content screening (HCS) platform using hiPSC-derived nociceptors to identify analgesics targeting the peripheral nervous system. These cells, cultured on multi-well microelectrode arrays, achieved nearly 100% active electrodes by week 2, maintaining stable activity for at least 2 weeks. After 28 days, we assessed drug effects on neuronal activity, achieving strong assay performance (robust Z' > 0.5). Pharmacological tests confirmed responses to key analgesic targets, including ion channels (Nav, Cav, Kv, and TRPV1), neurotransmitter receptors (AMPAR and GABA-R), and kinase inhibitors (tyrosine and JAK1/2). Transcriptomic analysis validated target expression, though levels differed from primary human DRG cells. The platform was used to screen over 700 natural compounds, demonstrating its potential for analgesic discovery. This HCS platform facilitates the rapid discovery of uncharacterized analgesics, reducing preclinical-to-human translation failure.

Keywords

CP: Stem cell; DRG; analgesic discovery; chronic pain; hiPSC; high-content screening; human induced pluripotent stem cell; nociceptor.

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