{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:24:16Z","timestamp":1760235856376,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuronal morphological changes in the epidermis are considered to be one of causes of abnormal skin sensations in dry skin-based skin diseases. The present study aimed to develop an in vitro model optimised for human skin to test the external factors that lead to its exacerbation. Human-induced pluripotent stem cell-derived sensory neurons (hiPSC-SNs) were used as a model of human sensory neurons. The effects of chemical substances on these neurons were evaluated by observing the elongation of nerve fibers, incidence of blebs (bead-like swellings), and the expression of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2). The nerve fiber length increased upon exposure to two common cosmetic preservatives\u2014methylparaben and phenoxyethanol\u2014but not to benzo[a]pyrene, an air pollutant at the estimated concentrations in the epidermis. Furthermore, the incidence of blebs increased upon exposure to benzo[a]pyrene. However, there was a decrease in the expression of NMNAT2 in nerve fibers, suggesting degenerative changes. No such degeneration was found after methylparaben or phenoxyethanol at the estimated concentrations in the epidermis. These findings suggest that methylparaben and phenoxyethanol promote nerve elongation in hiPSC-SNs, whereas benzo[a]pyrene induces nerve degeneration. Such alterations may be at least partly involved in the onset and progression of sensitive skin.<\/jats:p>","DOI":"10.3390\/ijms221910525","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T08:27:44Z","timestamp":1632904064000},"page":"10525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel In Vitro Assay Using Human iPSC-Derived Sensory Neurons to Evaluate the Effects of External Chemicals on Neuronal Morphology: Possible Implications in the Prediction of Abnormal Skin Sensation"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8632-8899","authenticated-orcid":false,"given":"Masahiko","family":"Satoh","sequence":"first","affiliation":[{"name":"FANCL Research Institute, FANCL Corporation, 12\u201313 Kamishinano Totsuka, Yokohama 244-0806, Kanagawa, Japan"},{"name":"Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamie","family":"Suzuki","sequence":"additional","affiliation":[{"name":"FANCL Research Institute, FANCL Corporation, 12\u201313 Kamishinano Totsuka, Yokohama 244-0806, Kanagawa, Japan"},{"name":"Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuhito","family":"Sakurai","sequence":"additional","affiliation":[{"name":"FANCL Research Institute, FANCL Corporation, 12\u201313 Kamishinano Totsuka, Yokohama 244-0806, Kanagawa, Japan"},{"name":"Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3606-245X","authenticated-orcid":false,"given":"Sumika","family":"Toyama","sequence":"additional","affiliation":[{"name":"Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yayoi","family":"Kamata","sequence":"additional","affiliation":[{"name":"Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"},{"name":"Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Kondo","sequence":"additional","affiliation":[{"name":"FANCL Research Institute, FANCL Corporation, 12\u201313 Kamishinano Totsuka, Yokohama 244-0806, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Suga","sequence":"additional","affiliation":[{"name":"Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"},{"name":"Department of Dermatology, Juntendo Urayasu Hospital, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1254-1803","authenticated-orcid":false,"given":"Mitsutoshi","family":"Tominaga","sequence":"additional","affiliation":[{"name":"Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"},{"name":"Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0644-0504","authenticated-orcid":false,"given":"Kenji","family":"Takamori","sequence":"additional","affiliation":[{"name":"Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"},{"name":"Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"},{"name":"Department of Dermatology, Juntendo Urayasu Hospital, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmed.2019.00108","article-title":"Role of keratinocytes in sensitive skin","volume":"6","author":"Talagas","year":"2019","journal-title":"Front. 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