Mesenchymal stem cell-derived Extracellular vesicles as a biological drug delivery system for Alzheimer’s disease

Introduction Extracellular vesicles are lipid membrane structures with the biological component which are secret from various cells such as mesenchymal stem cells (MSc) naturally and can pass through biological barriers for drug delivery approaches. Recent progresses in the manipulation of EVs have become these biological cargoes to interesting subjects in neurological disease therapy such as Alzhimer. Objectives Alzimer is caused by aggregation of beta amyloid sheets in the brain. Extracellular vesicles can be loaded with nepilysin which is an active enzyme in clearance of the aggregated and be used in Alzimer s disease therapy. Methods In order to purify and use EVs as a drug delivery system, MSc were isolated and expanded from rat femur. EVs were isolated from MSCs supernatant with ultracentrifugation in 100,000 g for 1h. Size and concentration of separated vesicles were evaluated with scanning electron microscopy (SEM), dynamic light scattering (DLS) and western blotting. Then, EVs were loaded with neprilysin by sonication. neprilysin loaded EVs were analyzed with high-performance liquid chromatography (HPLC). Results MS cells were established by stemness quality tests through differentiation potency to osteogenic and adipogenic cells. Furthermore, EVs were confirmed with specific markers analysis by flow cytometry and shape integrity and hemogenicity with SEM and DLS in size rang 30-300 nm. Isolated EVs were identified with western blotting for CD63 specific marker. Conclusion These loaded EVs can be used in the therapeutic investigation in animal models of Alzheimer’s disease through intranasal administration or engineered to target cells directly and increase drug delivery efficacy with different strategies

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Cartilage tissue engineering ، Scaffold ، Combinational methods of scaffold fabrication ، 3D print