Derivation of peripheral nociceptive, mechanoreceptive, and proprioceptive sensory neurons from the same culture of human pluripotent stem cells

Saito-Diaz K, Street JR, Ulrichs H, Zeltner N

Stem Cell Reports, 2021


The authors developed a protocol for deriving three, functional peripheral sensory neuron (SN) subtypes: nociceptors, mechanoreceptors, and proprioceptors from human pluripotent stem cells (hPSCs) that mimic subtypes in the dorsal root ganglion. The protocol yielded electrically active sensory neurons that responded to specific stimuli and is useful for studying disease phenotypes affecting SNs such as FD using patient-derived iPSCs. 

This protocol outlines a method of SN generation that went through the appropriate developmental stages and had the molecular characterization of SN subtypes mimicking DRG neuronal composition efficiently.  Late stage analysis of the hESC-derived SNs was evaluated using electrophysiology with Axion's multielectrode array platform.  Spontaneous neural activity was recorded between day 25 and 80.  The activity peaked at day 65 when firing and bursting was at its highest.  Synchronous bursting was not observed but it is unsure if PNS neurons form networks.  Functional responses of the derived SNs was tested: nociceptors increased firing rate after the application of nociceptor agonists such as capsaicin; mechanoreceptors increased firing rate after an increase of hypo-osomotic medium.  Replating SNs were found to be electrically active showing that functional SN can be maintained for long-term studies.