en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;"><span style="font-size:14px;"><span style="font-family:Tahoma;"><span style="line-height:2;"><strong>Introduction</strong>: Numerous studies have shown the positive effects of rosmarinic acid on the nervous system.Rosmarinic acid as a herbal compound with anti-inflammatory effects can prevent thedestructive effect of inflammation on the nervous system. Furthermore, various studies haveemphasized the advantages of three-dimensional (3D) culture over the two-dimensional (2D) culture of cells.&nbsp;<br> <strong>Methods</strong>: In this study, thermosensitive chitosan (CH)-based hydrogel as a 3D scaffoldwith the combination of chitosan, beta-glycerol phosphate and hydroxyl ethyl cellulose (CH-GP-HEC) loaded with rosmarinic acid was used to induce neuronal differentiation in humanWharton jelly stem cells. Also, cells were divided into eight groups to evaluate the effect of 3Dcell culture and to compare gene expression in different induction conditions.<br> <strong>Results</strong>: The results ofgene expression analysis showed the highest expression of neuronal markers in Whartons jelly derived mesenchymal stem cells (WJMSCs) cultured in chitosan, beta-glycerol phosphate and hydroxyl ethyl cellulose (ch-gp-hec) loaded with differentiation medium androsmarinic acid. According to the results of gene expression, rosmarinic acid alone has a positiveeffect on the induction of expression of neural markers. This positive effect is enhanced by cellculture in 3D conditions.&nbsp;<br> <strong>Conclusion</strong>: This study shows that rosmarinic acid can be considered an inexpensiveand available compound for use in neural tissue engineering. The results of this study indicatethat rosmarinic acid can be considered a cheap and available compound for use in neural tissueengineering.</span></span></span></div> Rosmarinic acid, Neural differentiation, Hydrogel, Chitosan (CH), Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) 117 128 http://bcn.iums.ac.ir/browse.php?a_code=A-10-2596-1&slc_lang=en&sid=1 Mohsen Salmanvandi 13700319475328460044428 13700319475328460044428 No Department of Material Engineering, Najafabad Branch, Islamic Azad University, Najafabad, Iran. Seyed Mohammad Amin Haramshahi 13700319475328460044429 13700319475328460044429 No Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. ; Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Elahe Mansouri 13700319475328460044430 13700319475328460044430 No Laboratory of Research and Development of Tissue Engineering Products-Hazrat Fatemeh hospital, Iran University of Medical Sciences, Tehran, Iran. Akram Alizadeh alizadehbio@gmail.com 13700319475328460044431 13700319475328460044431 Yes Department of Tissue Engineering and Applied Cell Sciences, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.