Table 2.
Stem cell differentiation protocols for human sensory neurons/nociceptors and their use in modelling painful pathologies
| Original cells | Resulting cellsa | Exogenous factors | Disease modelling | Reference |
|---|---|---|---|---|
| Direct induction | ||||
| Fibroblasts (mouse/human) | Nociceptive sensory neurons (iNoc) | Ascl1, Myt1l, Ngn1, Isl1, Klf7 | Familial dysautonomia | Wainger et al.100 |
| Fibroblasts | Induced peripheral sensory neurons (iSNs) | Brn3a, Ngn1 or Ngn2 | – | Blanchard et al.101 |
| IPSC protocols | ||||
| IPSCs (or ESCs) | IPSC-derived nociceptors | OKSM factors, LDN19318, SB431542, CHIR99021, SU5402, DAPT, Y27632, EGF, FGF, NTFs (Chamber’s protocol) | – | Chambers et al.102 |
| Migraine | Pettingill et al.103 | |||
| IPSCs | IPSC-derived nociceptors | Chamber’s protocol + minor modifications | IEM | Meents et al.104 |
| IPSCs | IPSC-derived nociceptors | Chamber’s protocol + minor modifications | Small fibre neuropathy | Namer et al.105 |
| IPSCs | IPSC-derived nociceptors | Chamber’s protocol + minor modifications | CIP | McDermott et al.106 |
| IPSCs | IPSC-derived peripheral sensory neurons | Chamber’s protocol + minor modifications | Varicella-zoster virus infection | Lee et al.107 |
| IPSCs (from PBMCs) | IPSC-derived peripheral sensory neurons | Chamber’s protocol + minor modifications | IEM | Cao et al.108 |
| IPSCs | IPSC-derived peripheral sensory neurons | Chamber’s protocol + minor modifications | Remyelination therapy | Cai et al.109 |
| IPSCs (from PBMCs) | IPSC-derived peripheral sensory neurons | Chamber’s protocol + minor modifications | IEM | Mis et al.110 |
| IPSCs | IPSC-derived peripheral sensory mechanoreceptors | Chamber’s protocol + minor modifications | – | Guimarães et al.111 |
| IPSCs | IPSC-derived proprioceptive neurons | Chamber’s protocol + minor modifications | Afferent ataxia | Dionisi et al.112 |
| IPSCs | IPSC-derived trigeminal neurons | Chamber’s protocol + minor modifications | HSV-1 infection | Zimmer et al.113 |
| IPSCs | Peripheral mechanoreceptors | OKSM factors, NTFs | – | Schrenk-Siemens et al.114 |
| IPSCs | NC-iSN mechanosensory neurons | OKSM factors, Y27632, SB431542, Brn3a, Ngn2, NTFs | Piezo2 channelopathy | Nickolls et al.115 |
| IPSCs | IPSC-NCd sensory neurons | Noggin, LDN193189, SB431542, Y27632, NTFs | – | Umehara et al.116 |
| ESC/other protocols | ||||
| hEPI-NCSC | Peptidergic nociceptive Sensory neurons | SHH, CHIR99021, LDN193189, DAPT, HGF, NTFs | – | Wilson et al.117 |
| iNPCs | Peripheral sensory neurons (iSNs) | LDN193189, SB431542, CHIR9902, DAPT, SU5402, NTFs | Chemotherapy-induced neuropathy | Vojnits et al.118 |
| ESCs | Peripheral sensory neurons | LDN193189, SB431542, CHIR9902, DAPT, SU5402, Y27632, NTFs | Peripheral nerve injury | Jones et al.119 |
| ESCs | Peripheral sensory neurons | SB431542, CHIR9902, BMP2, Y27632, NTFs | – | Alshawaf et al.120 |
A substantial number of IPSC protocols are largely based on Chambers et al.102 and have since undergone small modifications; for protocol adaptation refer to each original publication. CIP = congenital insensitivity to pain; ESC = embryonic stem cell; hEPI-NCSC = human epidermal neural crest stem cells; iNPC = induced neural progenitor cells; iSNs = induced sensory neurons; NCd = neural crest-derived; NC-iSN = neural crest derived induced sensory neurons; NTF = neurotrophic factors; PBMCs = peripheral blood mononuclear cells.
a
Note that ‘Resulting cells’ is the nomenclature used by each original publication.