Immortalized human dorsal root ganglion cells differentiate into neurons with nociceptive properties

A renewable source of human sensory neurons would greatly facilitate basic research and drug development. We had established previously conditionally immortalized human CNS cell lines that can differentiate into functional ne urons (Sah et al., 1997). We report here the development of an immortalized human dorsal root ganglion (DRG) clonal cell line, HD10.6, with a tetracyc line-regulatable v-myc oncogene. In the proliferative condition, HD10.6 cel ls have a doubling time of 1.2 d and exhibit a neuronal precursor morpholog y. After differentiation of clone HD10.6 for 7 d in the presence of tetracy cline, v-myc expression was suppressed, and >50% of the cells exhibited typ ical neuronal morphology, stained positively for neuronal cytoskeletal mark ers, and fired action potentials in response to current injection. Furtherm ore, this cell line was fate-restricted to a neuronal phenotype; even in cu lture conditions that promote Schwann cell or smooth muscle differentiation of neural crest stem cells, HD10.6 differentiated exclusively into neurons . Moreover, differentiated HD10.6 cells expressed sensory neuron-associated transcription factors and exhibited capsaicin sensitivity. Taken together, these data indicate that we have established an immortalized human DRG cel l line that can differentiate into sensory neurons with nociceptive propert ies. The cell line HD10.6 represents the first example of a human sensory n euronal line and will be valuable for basic research, as well as for the di scovery of novel drug targets and clinical candidates.