Evaluation of the immune-modulatory, anti-oxidant, proliferative, and anti-apoptotic effects of nano-silymarin on mesenchymal stem cells isolated from multiple sclerosis patients' adipose tissue sources
Fahimeh Lavi Arab, Forouzan Yousefi, Mahmoud Reza Jaafari, Arezoo Rajabian, Hassan Dana, Nafiseh Tabasi, Saeed Behboodifar, Arezoo Faridzadeh, Mahmoud Mahmoudi
Abstract
Silymarin (SL) has a long history of use for the treatment of a variety of diseases, but several limitations, such as poor bioavailability and negligible solubility, have restricted its successful translation in a clinical setting. However, the nano-micelle delivery system is a highly reproducible method which capable of improving poor-water solubility and bioavailability of free-SL. Mesenchymal stem cells (MSCs) are multipotent cells proficient in tissue renewal and regeneration. MSCs have similar properties to SL including immunomodulatory, antioxidant, and neuroprotective effects. Here, we show that nano-SL (1 and 2.5) increased AD-MSCs proliferation and protected from apoptosis. Our findings indicated that the levels of anti-inflammatory agents including IL-10, IL-4, FOXp3 and TGF-B mRNA expression were significantly upregulated in nano-SL-treated MSCs along with downregulated mRNA expression of pro-inflammatory cytokines (IL-6, IL-17). We identified that nano-SL elevated the T-regulatory (Treg) population (1 and 2.5 µM) and superoxide dismutase activity (2.5 µM) while decreasing nitrite oxide content. Conclusively, combinatorial therapy by nano-SL and MSCs may be useful for MS patients who are receiving MSCs for treatment.