J Human Gen Genom. 2019 December; 3(2):e111835. Published online 2021 January 2. doi: 10.5812/jhgg.111835. Research Article Evaluation of Human Mesenchymal Stem Cells Differentiation to Neural Cells on Polycaprolactone Nanofiber Scaffolds Seyedeh Sara Karimian 1, * , Saeid Kaviani 2 and Masoud Soleimani 2 1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran 2 Department of Hematology, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran, Iran * Corresponding author: Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. Tel: +98-9123309710. Email: sarakmn1983@gmail.com Received 2020 December 16; Accepted 2020 December 21. Abstract Differentiation of human mesenchymal stem cells (hMSC) to neural cells on Nano-scaffolds is a promising method for the treatment of the damaged nervous system through bionanomaterial-cell transplantation. The hMSC’s multipotential features have been dis- covered in various tissue engineering researches. This investigation shows the in-vitro development and neural differentiation of hMSC in 3D and 2D environments. The 3D environment which used in this study is nanofibrous polycaprolactone (PCL). The differ- entiation potential of mesenchymal stem cells (MSCs) to neural cells, on the random polycaprolactone (PCL) nanofibrous scaffolds, and tissue plate was examined. Researches have proved that interaction of extracellular nanofibrous matrix with in-vivo cells, gives mechanical maintenance to the cells and plays a functional role in the control of cellular behaviour. Stem cells are developing as a fundamental tool in the evolution of tissue engineering and regenerative medication. PCL characterization was determined employing scanning electron microscopy (SEM). Agents like, retinoic acid, epidermal growth factor (EGF), fibroblast growth factor (FGF-2), and Ibmx, which they are neural inducing agents, added in DMDM/F12 to differentiate MSCs to neural cells. Reproduction of mesenchymal cells on PCL nanofibrous scaffolds and neural morphology revealed through a scanning electron microscope (SEM) and optical microscope outcomes. The differentiated mesenchymal cells on nanofibrous scaffolds express neural gene markers in- cluding; β- tubulin III and Map2 on the day of 14. Our investigation recommends the potential usage of differentiated neural cells from hMSCs on Nano-scaffolds toward the improvement of neural cells. This study conducted in 2011. Keywords: Human Mesenchymal Stem Cells, Neural Cells, Polycaprolactone Scaffolds, Tissue Engineering, Cell Therapy 1. Background Repairing the neural damages employing nerve tissue engineering is one of the most promising approaches. In neural tissue engineering, nano-scaffolds use as an extra- cellular matrix and their efficacy has proved by various re- searches. Directing role of biomaterial substrates in the differentiation of mesenchymal stem cells (MSCs) has been proven (1, 2). MSCs obtained of bone marrow (BM) are non-hematopoietic stem cells, containing the ability to differentiate into various ectodermal (neural), mesenchy- mal (adipocyte, chondrocytes), and endodermal (hepato- cytes) tissue cells (3). MSC is one of the accessible cell ori- gins of the body, containing the most simple clinical tech- nique of culturing with a high self-regeneration role (4). New researches have demonstrated the capability usages of MSCs obtained of bone marrow, which differentiated on the nano-scaffolds, to tissue renewal (5). Osteoblasts or chondrocytes, which differentiated from MSCs on the 3D nanofiber matrix, were evaluated in the various studies (6, 7). Differentiation of MSCs on the electrospun nanofiber scaffolds has considered in many studies. Scaffolds for tis- sue regeneration are essential as they provide suitable re- quirements for cell resistance regeneration and differenti- ation and tissues’ expansion for desired tissue engineering goals (8). Contemporary researches have aimed to build and develop suitable scaffold for tissue reconstruction (9). This examination evaluated the efficacy of polycaprolac- tone (PCL) nanofiber matrices produced via the phase sep- aration technique as a scaffold for neural tissue reforma- tion (10). PCL presented as a biomaterial for medicine and drug delivery method (11, 12). Furthermore, PCL is a fab- ricated environment-friendly and non-toxic polymer that has considered a biomaterial for nerve tissue engineering as its convenient form appearance. Although, its low hy- drophilicity regularly performs in limited cell adhesion on scaffolds. Copyright © 2021, Journal of Human Genetics and Genomics. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.