Sertoli Cells Avert Neuroinflammation-Induced Cell Death and Improve Motor Function and Striatal Atrophy in Rat Model of Huntington Disease Houssein Ahmadi 1 & Mahdi Eskandarian Boroujeni 2 & Yousef Sadeghi 1 & Mohammad Amin Abdollahifar 1 & Fariba Khodagholi 3 & Gholam Houssein Meftahi 4 & Mohammadmehdi Hadipour 4 & Amir-Hossein Bayat 5 & Fatemeh Shaerzadeh 6 & Abbas Aliaghaei 1 Received: 20 February 2018 /Accepted: 27 March 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract Huntington’s disease (HD) is a genetically heritable disorder, linked with continuing cell loss and degeneration mostly in the striatum. Currently, cell therapy approaches in HD have essentially been focused on replenishing or shielding cells lost over the period of the disease. Herein, we sought to explore the in vitro and in vivo efficacy of primary rat Sertoli cells (SCs) and their paracrine effect against oxidative stress with emphasis on HD. Initially, SCs were isolated and immunophenotypically charac- terized by positive expression of GATA4. Besides, synthesis of neurotrophic factors of glial cell-derived neurotrophic factor and VEGF by SCs were proved. Next, PC12 cells were exposed to hydrogen peroxide in the presence of conditioned media (CM) collected from SC (SC-CM) and cell viability and neuritogenesis were determined. Bilateral striatal implantation of SC in 3- nitropropionic acid (3-NP)-lesioned rat models was performed, and 1 month later, post-graft analysis was done. According to our in vitro results, the CM of SC protected PC12 cells against oxidative stress and remarkably augmented cell viability and neurite outgrowth. Moreover, grafted SCs survived, exhibited decreases in both gliosis and inflammatory cytokine levels, and amelio- rated motor coordination and muscle activity, together with an increase in striatal volume as well as in dendritic length of the striatum in HD rats. In conclusion, our results indicate that SCs provide a supportive environment, with potential therapeutic benefits aimed at HD. Keywords Transplantation . Huntington . Striatum . Sertoli cells . Neuroprotection Introduction Huntington’s disease (HD) is a heritable disorder, genetically instigated by insertion mutation of huntingtin gene (Htt), linked with continuing cell loss and degeneration mostly in the striatum and neocortex (Bates et al. 2014; Leegwater-Kim and Cha 2004; MacDonald et al. 1993). Currently, cell therapy approaches in HD have essentially been focused on replenishing or shielding cells lost over the period of the disease (Clelland et al. 2008). Sertoli cells (SCs) as the nurturing cells are located within sem- iniferous tubules of the testis and provide an immunoprivileged milieu for the growing spermatogonia. SCs have been demon- strated to locally immunoprotect co-implanted cells (Shamekh et al. 2006; Korbutt et al. 1997; Sanberg et al. 1996; Suarez- Pinzon et al. 2000; Yang et al. 2002; Willing et al. 1999a), im- prove cell proliferation and neuronal induction (Shamekh et al. 2008; Hemendinger et al. 2005), and survive for prolonged pe- riods of time once grafted (Dufour et al. 2008). Prior works have * Abbas Aliaghaei aghaei60@gmail.com 1 Department of Cell Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 Department of Stem Cells and Regenerative Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran 3 Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4 Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran 5 Department of Neuroscience, Saveh University of Medical Sciences, Saveh, Iran 6 Department of Neuroscience, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32611, USA Journal of Molecular Neuroscience https://doi.org/10.1007/s12031-018-1062-x