{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:55:49Z","timestamp":1790258149063,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T00:00:00Z","timestamp":1583280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Regenerative medicine is a rapidly expanding area in research and clinical applications. Therapies involving the use of small molecule chemicals aim to simplify the creation of specific drugs for clinical applications. Adult mesenchymal stem cells have recently shown the capacity to differentiate into several cell types applicable for regenerative medicine (specifically neural cells, using chemicals). Valproic acid was an ideal candidate due to its clinical stability. It has been implicated in the induction of neural differentiation; however, the mechanism and the downstream events were not known. In this study, we showed that using valproic acid on adult mesenchymal stem cells induced neural differentiation within 24 h by upregulating the expression of suppressor of cytokine signaling 5 (SOCS5) and Fibroblast growth factor 21 (FGF21), without increasing the potential death rate of the cells. Through this, the Janus Kinase\/Signal Transducer and Activator of Transcription (JAK\/STAT) pathway is downregulated, and the mitogen-activated protein kinase (MAPK) cascade is activated. The bioinformatics analyses revealed the expression of several neuro-specific proteins as well as a range of functional and structural proteins involved in the formation and development of the neural cells.<\/jats:p>","DOI":"10.3390\/cells9030619","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T10:46:08Z","timestamp":1583318768000},"page":"619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Valproic Acid Promotes Early Neural Differentiation in Adult Mesenchymal Stem Cells Through Protein Signalling Pathways"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4067-220X","authenticated-orcid":false,"given":"Jerran","family":"Santos","sequence":"first","affiliation":[{"name":"Advanced Tissue Regeneration &amp; Drug Delivery Group, School of Life Sciences, University of Technology Sydney, P.O. Box 123, Broadway, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Hubert","sequence":"additional","affiliation":[{"name":"Advanced Tissue Regeneration &amp; Drug Delivery Group, School of Life Sciences, University of Technology Sydney, P.O. Box 123, Broadway, NSW 2007, Australia"},{"name":"Ecole Nationale Sup\u00e9rieure D\u2019agronomie et des Industries Alimentaires (ENSAIA), Universit\u00e9 de Lorraine, 2 Avenue de la For\u00eat de Haye, 54505 Vand\u0153uvre-l\u00e8s-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0867-9586","authenticated-orcid":false,"given":"Bruce K","family":"Milthorpe","sequence":"additional","affiliation":[{"name":"Advanced Tissue Regeneration &amp; Drug Delivery Group, School of Life Sciences, University of Technology Sydney, P.O. Box 123, Broadway, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,4]]},"reference":[{"key":"ref_1","first-page":"221","article-title":"Differentiation of human adipose-derived adult stem cells into neuronal tissue: Does it work?","volume":"77","author":"Bonatto","year":"2009","journal-title":"Differ. Res. Biol. Divers."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/1097-4547(20000815)61:4<364::AID-JNR2>3.0.CO;2-C","article-title":"Adult rat and human bone marrow stromal cells differentiate into neurons","volume":"61","author":"Woodbury","year":"2000","journal-title":"J. Neurosci. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Santos, J., Milthorpe, B.K., Herbert, B.R., and Padula, M.P. (2017). Proteomic Analysis of Human Adipose Derived Stem Cells during Small Molecule Chemical Stimulated Pre-neuronal Differentiation. Int. J. 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