A Histological Study of the Impact of Bone Marrow Mesenchymal Stem Cells- Derived Exosomes on the Corpus Callosum in a Cuprizone-Induced Mouse Model of Multiple Sclerosis

Introduction: A chronic demyelinating disease that affects millions of peoples worldwide is multiple sclerosis (MS). There are currently no remyelination therapy for this disease, and exosomes are being explored as an alternative.Aim: to study how exosomes generated from bone marrow mesenchymal stem cells (BMSCs) affect the corpus callosum structure in male mice with cuprizone model of MS. Materials and methods: Forty-seven adult male mice were used in this work. Exosomes were isolated and extracted from five mice. Forty-two adult male mice were split into two equal groups randomly: Group I (Control): divided into three equal subgroups. Group II (Cuprizone-treated): which was treated with cuprizone, was given 400 mg/kg/day of the drug orally every day for 8 weeks. Then equally divided into three subgroups. Subgroup IIA: sacrificed 24 hours following the final cuprizone dosage. Subgroup IIB (Recovery): left without treatment for further 4 weeks, then were sacrificed. Following the final dose of cuprizone, subgroup IIC (exosomes treated): got a single intravenous injection of exosomes into tail vein, and were sacrificed 4 weeks later. After scarification, brains tissue were prepared using histological, immune-histochemical methods and histomorphometric studies.Results: Histological analysis of corpus callosum in subgroups IIA & IIB showed damaged nerve fibers by H&E with multiple vacuoles. Improvement of these changes was noticed in subgroup IIC. By luxol fast blue, nerve fibers stained deep blue in subgroup IIC & control group. While, in subgroups IIA & IIB, nerve fibers stained faint blue. Subgroups IIA & IIB showed marked rise in the number of GFAP and Iba1 positive cells.Conclusions: In the cuprizone model of MS, exosomes were demonstrated to improve demyelination of mice's corpus callosum. Exosomes may therefore offer a novel approach to MS treatment.