Journal
STEM CELL REPORTS
Volume 5, Issue 3, Pages 305-313Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2015.07.010
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Funding
- Johannes and Frieda Marohn-Foundation [Win/2012]
- German Federal Ministry of Education and Research (BMBF) [01GQ113]
- Bavarian Ministry of Sciences, Research and the Arts in the framework of the Bavarian Molecular Bio-systems Reseach Network
- ForIPS network
- Interdisciplinary Center for Clinical Research (University Hospital Erlangen)
- Bavarian Research Foundation [PIZ-180-10]
- German-Israeli-Foundation (GIF) [1091-27.1/2010]
- German Research Association [DFG LA2740/2-1, NA 970 1/1, INST 90/675-1 FUGG]
- Jurgen Manchot Stiftung
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Human pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptive neurons expressed respective markers and showed tetrodotoxin-sensitive (TTXs) and -resistant (TTXr) voltage-gated sodium currents in patch-clamp experiments. In contrast to their counterparts from rodent dorsal root ganglia, TTXr currents of hPSC-derived nociceptors unexpectedly displayed a significantly more hyperpolarized voltage dependence of activation and fast inactivation. This apparent discrepancy is most likely due to a substantial expression of the developmentally important sodium channel NAV1.5. In view of the obstacles to recapitulate neuropathic pain in animal models, our data advance hPSC-derived nociceptors as a better model to study developmental and pathogenetic processes in human nociceptive neurons and to develop more specific small molecules to attenuate pain.
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