The opioid crisis highlights the urgent need for novel non-addictive pain medications, as well as improved treatments for opioid addiction and overdose. To this end, human biology-focused model systems are required for target identification/validation and pharmacological testing that hold promise for more successful clinical results as compared to traditional approaches. Therefore, critical human cell-based screening technologies are being established in order to enable discovery of novel therapeutics for the opioid crisis. The use of the iPSC technology allows the generation of human sensory neurons and other cell types relevant to pain, addiction, and overdose. The NCATS Stem Cell Translation Laboratory (SCTL) has developed a scalable and fully automated protocol to generate pure cultures of sensory neurons (nociceptors) in large quantities under chemically defined conditions. The available screening capabilities, scalable production of the most relevant human cell types, and their real-time functional characterization provide unprecedented opportunities to, in collaboration with external pain/addiction experts, to identify probe/lead compounds with improved predictivity for in vivo human effects. Over the past year, the SCTL has produced large quantities of pure iPSC-derived nociceptors that have been provided to external collaborators with expertise in pain, addiction and overdose. Through these external collaborations, key nociceptor markers and ion channels (e.g. NAV1.8) that play important roles in pain pathways have been validated and now provide unprecedented opportunities and resources for the research community. In order to provide the community with viable iPSC-derived cells, the SCTL conducted research on efficient biobanking and cell viability and developed a protocol that allows shipment of cryopreserved cells to external collaborators. Development, validation, and utilization of additional cell types relevant to pain, opioid-use disorder, and overdose are currently on-going, with the goal of broadly disseminating these cell types to scientists with the goal to broadly leverage the use of human iPSC-derived cell types as part of new preclinical models. As a consequence, a larger group of scientists will be exploiting the iPSC technology for translational studies in pain, opioid use disorder, and overdose, increasing the likelihood of translational success in therapeutic development for these HEAL-relevant indications.
