Sertoli Cells Avert Neuroinflammation-Induced Cell Death and Improve Motor Function and Striatal Atrophy in Rat Model of Huntington Disease

Huntington’s diseases (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. Materials and Methods: Herein, we sought to explore the in vitro and in vivo efficacy of primary rat sertoli cells (SC) and their paracrine effect against oxidative stress with emphasis on HD. Initially, SC were isolated and immunophenotypically characterized by positive expression of GATA4. Besides, synthesis of neurotrophic factors of GDNF and VEGF by SC 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 neurogenesis were determined. Bilateral striatal implantation of SC in 3-nitropropionic acid (3-NP) lesioned rat models was performed and one month later, post-graft analysis wasdone. Results: According to our in vitro results, CM of SC protected PC12 cells against oxidative stress and remarkably augmented cell viability and neurite outgrowth. Moreover, grafted SC survived, exhibited decreases in both gliosis and inflammatory cytokines levels, and ameliorated motor coordination and muscle activity, together with an increase in striatal volume as well as in dendritic length of the striatum in HD rats.Conclusion: In conclusion, our results indicate that SC provide a supportive environment, with potential therapeutic benefits aimed at HD.