{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T01:32:18Z","timestamp":1789263138338,"version":"build-2803163510"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100023520","name":"Department of Defense Education Activity","doi-asserted-by":"publisher","award":["W81XWH-16-1-0102"],"award-info":[{"award-number":["W81XWH-16-1-0102"]}],"id":[{"id":"10.13039\/100023520","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NF Michigan"},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["0216084"],"award-info":[{"award-number":["0216084"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMR-1229284"],"award-info":[{"award-number":["DMR-1229284"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["0922912"],"award-info":[{"award-number":["0922912"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Neurofibromatosis Type 1 (NF1) is a complex genetic disorder characterized by the development of benign neurofibromas, which can cause significant morbidity in affected individuals. While the molecular mechanisms underlying NF1 pathogenesis have been extensively studied, the development of effective therapeutic strategies remains a challenge. This paper presents the development and validation of a novel biomaterial testing model to enhance our understanding of NF1 pathophysiology, disease mechanisms and evaluate potential therapeutic interventions. Our long-term goal is to develop an invitro model of NF1 to evaluate drug targets. We have developed an <jats:italic>in vitro<\/jats:italic> system to test the cellular behavior of NF1 patient derived cells on electroconductive aligned nanofibrous biomaterials with electrical stimulatory cues. We hypothesized that cells cultured on electroconductive biomaterial will undergo morphological changes and variations in cell proliferation that could be further enhanced with the combination of exogenous electrical stimulation (ES). In this study, we developed electrospun Hyaluronic Acid\u2013Carbon Nanotube (HA-CNT) nanofiber scaffolds to mimic the axon\u2019s topographical and bioelectrical cues that influence neurofibroma growth and development. The cellular behavior was qualitatively and quantitively analyzed through immunofluorescent stains, Alamar blue assays and ELISA assays. Schwann cells from NF1 patients appear to have lost their ability to respond to electrical stimulation in the development and regeneration range, which was seen through changes in morphology, proliferation and NGF release. Without stimulation, the conductive material enhances NF1 SC behavior. Wild-type SC respond to electrical stimulation with increased cell proliferation and NGF release. Using this system, we can better understand the interaction between axons and SC that lead to tumor formation, homeostasis and regeneration.<\/jats:p>","DOI":"10.1371\/journal.pone.0308207","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T17:32:47Z","timestamp":1723051967000},"page":"e0308207","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Electrical stimulation of Schwann cells on electrospun hyaluronic acid carbon nanotube fibers"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6049-4417","authenticated-orcid":true,"given":"Judy","family":"Senanayake","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond R.","family":"Mattingly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0205-6449","authenticated-orcid":true,"given":"Harini G.","family":"Sundararaghavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,7]]},"reference":[{"issue":"1","key":"pone.0308207.ref001","doi-asserted-by":"crossref","first-page":"180106","DOI":"10.1038\/sdata.2018.106","article-title":"Pharmacological and genomic profiling of neurofibromatosis type 1 plexiform neurofibroma-derived schwann cells.","volume":"5","author":"M. Ferrer","year":"2018","journal-title":"Scientific Data"},{"issue":"3","key":"pone.0308207.ref002","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.jpeds.2011.08.051","article-title":"Pediatric plexiform neurofibromas: impact on morbidity and mortality in neurofibromatosis type 1","volume":"160","author":"C.E. Prada","year":"2012","journal-title":"J Pediatr"},{"issue":"2","key":"pone.0308207.ref003","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.stemcr.2019.01.001","article-title":"Reprogramming Captures the Genetic and Tumorigenic Properties of Neurofibromatosis Type 1 Plexiform Neurofibromas.","volume":"12","author":"M. Carri\u00f3","year":"2019","journal-title":"Stem Cell Reports"},{"issue":"Pt B","key":"pone.0308207.ref004","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.expneurol.2017.10.012","article-title":"Development of 3D culture models of plexiform neurofibroma and initial application for phenotypic characterization and drug screening","volume":"299","author":"J.M. Kraniak","year":"2018","journal-title":"Experimental neurology"},{"issue":"3","key":"pone.0308207.ref005","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/0896-6273(92)90270-N","article-title":"The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes","volume":"8","author":"M.M. Daston","year":"1992","journal-title":"Neuron"},{"issue":"3","key":"pone.0308207.ref006","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/(SICI)1098-2264(199903)24:3<283::AID-GCC15>3.0.CO;2-K","article-title":"Loss of NF1 allele in schwann cells but not in fibroblasts derived from an NF1-associated neurofibroma","volume":"24","author":"L. Kluwe","year":"1999","journal-title":"Genes, Chromosomes and Cancer"},{"issue":"32","key":"pone.0308207.ref007","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1038\/sj.onc.1210261","article-title":"Tumor microenvironment and neurofibromatosis type I: connecting the GAPs","volume":"26","author":"L.Q. Le","year":"2007","journal-title":"Oncogene"},{"issue":"2","key":"pone.0308207.ref008","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/jnr.490360212","article-title":"Modulation of the neurofibromatosis type 1 gene product, neurofibromin, during Schwann cell differentiation","volume":"36","author":"D.H. Gutmann","year":"1993","journal-title":"Journal of Neuroscience Research"},{"issue":"2","key":"pone.0308207.ref009","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1083\/jcb.111.2.645","article-title":"Angiogenic and invasive properties of neurofibroma Schwann cells","volume":"111","author":"S. Sheela","year":"1990","journal-title":"Journal of Cell Biology"},{"issue":"7","key":"pone.0308207.ref010","doi-asserted-by":"crossref","first-page":"110385","DOI":"10.1016\/j.celrep.2022.110385","article-title":"Modeling iPSC-derived human neurofibroma-like tumors in mice uncovers the heterogeneity of Schwann cells within plexiform neurofibromas","volume":"38","author":"H. Mazuelas","year":"2022","journal-title":"Cell Reports"},{"issue":"26","key":"pone.0308207.ref011","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1056\/NEJMoa1605943","article-title":"Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas","volume":"375","author":"E. 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Jessen","year":"2005","journal-title":"Nat Rev Neurosci"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0308207","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T17:33:13Z","timestamp":1723051993000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0308207"}},"subtitle":[],"editor":[{"given":"Jianxun","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,7]]},"references-count":38,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0308207","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,7]]}}}