Characterization of human induced nociceptors produced by a novel iPSC differentiation protocol for disease modeling

National Center For Advancing Translational Sciences

Investigators

Abstract

In this fiscal year, iPSC derived sensory neurons generated at NCATS were used to demonstrate that primary non-neuronal cells from mouse DRG support iPSC-derived sensory neurons. Co-cultures of iPSC derived nociceptors with non-neuronal DRG cells including Schwann cells and microglia positively affect the neuronal size, clustering and health of long-term culture (> 8 weeks). These results will facilitate long-term cell culture of iPSC derived nociceptors and support the notion that iPSC derived nociceptor may further mature in co-culture with non-neuronal cells. It was also demonstrated that our iPSC derived nociceptors can be utilized as a screening tool when combined with a PKA reporter assay developed at MIT in collaboration with BCH. Through a newly established research collaboration agreement our iPSC derived nociceptors will be utilized to further develop this screening platform to identify compounds that block PKA activity as potential drugs that prevent nociceptor sensitization in peripheral injury induced inflammatory pain. Additionally, after licensing our protocol CDI Fuji Film released the commercialization of iCell Sensory Neurons which are generated based on our differentiation protocol, making this cell type available to the research community. This fiscal year, the SCTL acquired an electrophysiology rig that allows for in-house patch clamp and functional validation of our iPSC-derived nociceptors generated using our original and new differentiation pipelines. Therefore, characterization by these external collaborators has not been required.