Recent advances for using human induced-pluripotent stem cells as pain-in-a-dish models of neuropathic pain

Characterization of human iPSC-derived sensory neurons and their functional assessment using multi electrode array

“…The expression levels of Brn3a, TRPM8, TRKB and MrgprX1 in hiPSC-derived sensory neurons were comparable to those in human DRG, whereas the others were lower than in hDRG. The reason some genes of hiPSC-derived sensory neurons showed lower expression than hDRG might be due to the immature nature of the hiPSC-derived sensory neurons 20 . Although we cultured them for a long time, the expression levels of Peripherin, TRPV1, TRPA1, Nav1.7, Nav1.8, H1R, and CGRP were not comparable to the ones in hDRG (Supplementary Fig.…”

Differentiation of peripheral sensory neurons from iPSCs derived from stem cells from human exfoliated deciduous teeth (SHED)

“…In addition to the entire PNS, sensory neurons differentiate from neural crest cells during embryogenesis ( Hall, 2009 ; Szobó& Mayor, 2018 ) from a portion of cells at the edge of the neural plate that starts to separate and migrate during the formation of the neural tube, leading to the origin of CNS cells ( de Lahunta et al, 2016 ). Our protocol differentiates sensory neurons from somatic cells that also originated from the neural crest ( Labau et al, 2022 ), and, as cells after reprogramming still carry their transcriptional signature, it is important that when working with iPSC technology, whenever possible, using the same embryonic origin of the cell source and the cell target of the study after the final differentiation is considered. An advantage presented is that the PSNs generated by this method do not present significant changes in their functionality according to variations in the final phase of the protocol, indicating that they are not as sensitive as those originating from fibroblasts ( Schwartzentruber et al, 2018 ; Umehara et al, 2020 ), although additional analyses are necessary to confirm this result.…”

“…In addition, sensory neurons have recently been described as very much affected during viral infections, like in the coronavirus disease of 2019 (COVID-19) pandemic, in which 80% of infected people manifested alterations in senses related to the peripheral nervous system (PNS), like ageusia (loss of sense of taste) and anosmia (loss of sense of smell) ( Cooper et al, 2020 ; Patel et al, 2020 ; Cunhados et al, 2021 ). Once again, sensorial stimuli seem to be affected in neurodevelopmental disorders, such as ASD and attention-deficit hyperactivity disorder (ADHD), in neuropathic pain, and specific sensory disorders, like sensory processing disorder (SPD) ( Koziol et al, 2011 ; Weiland et al, 2011 ; Hazen et al, 2014 ; Labau et al, 2022 ).…”

“…Neurons from the sensory system still face difficulties in differentiation protocols, which impact their use for in vitro modeling ( Labau et al, 2022 ). Sensory neuron differentiation protocols ( Chambers et al, 2012 ; Eberhardt et al, 2015 ; Guimarães et al, 2018 ; Schwartzentruber et al, 2018 ; Mis et al, 2019 ; Nickolls et al, 2020 ; Umehara et al, 2020 ) have been tested on more than 100 different human iPSC (hiPSC) strains, all derived from pulmonary, dermal fibroblasts, or blood, which are cells of mesenchymal origin ( LeBleu & Neilson, 2020 ).…”

Fifty years of pain research and clinical advances: highlights and key trends

“…Highlights include characterization of peripheral and central sensitization processes, 3,19,53 transcriptomic analyses of primary sensory and dorsal horn neurons 22,50 and nonneuronal cells, 32 and the development of induced pluripotent stem cell (iPSC)-derived nociceptors. 33 Many of these analyses are also expanding in human tissue. 45 A particularly notable rodent highlight was discovery of the spinoparabrachial pathway 8 and its connections with forebrain regions that process pain affect.…”