Anti-inflammatory Effects of Umbilical Cord Mesenchymal Stem Cell and Autologous Conditioned Serum on Oligodendrocyte, Astrocyte, and Microglial Specific Gene in Cuprizone Animal Model.

Abstract

Inflammation, myelin loss, astrocytosis, and microgliosis are pathological signs of the autoimmune and demyelinating disease known as multiple sclerosis (MS). Axonal and neuronal degenerations have basic molecular pathways. The remyelination process can be influenced by the secretome of mesenchymal stem cells due to their capacity for immunomodulation, differentiation, and neuroprotection. Microglial cells are divided into two subgroups: M1 and M2 phenotypes. A crucial component of the microglial function is the colony stimulating factor 1 receptor (CSF1R). We aimed to evaluate the immunomodulating effects of secretome and conditioned serum on the microglial phenotypes and improvement of demyelination in a cuprizone model of MS. The study used 48 male C57BL/6 mice, which were randomly distributed into 6 subgroups (n = 8), i.e., control, cuprizone, MSC (confluency 40% and 80%) secretome group, and blood derived conditioned serum (autologous and humanized). The animals were fed with 0.2% cuprizone diet for 12 weeks. Supplements were injected into the lateral tail vein using a 27-gauge needle every 3 days 500 μl per injection. At 14 days after transplantation, animals from each group were sacrificed and analyzed by Real time PCR. The results showed that the administration of MSC secretome can efficiently reduce expression of pro-inflammatory cytokines (IL-1, IL6 and TNF-α) in the corpus callosum; also, conditioned serum downregulated IL-1. Moreover, the oligodendrocyte-specific gene was upregulated by secretome and conditioned serum treatment. Also, the expression of microglial- specific gene was reduced after treatment. These findings demonstrated that the secretome isolated from MSCs used as a therapy decreased and increased the M1 and M2 levels, respectively, to control neuroinflammation in CPZ mice. In conclusion, the current study showed the viability of devising a method to prepare suitable MSCs and secreted factor to cure neurodegenerative diseases, as well as the capability of regulating MSC secretome patterns by manipulating the cell density.