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Mesenchymal Stem Cells

The brain homeostasis is tightly maintained by the BBB, circulating immunocytes such as macrophages, and distinct subsets of lymphocytes. These immunocytes utilize specialized mechanisms to penetrate the BBB without compromising its structural integrity. Stem cells, particularly mesenchymal stem cells, can also penetrate the BBB. These cells show tropism for brain tumors in animal models. However, their transmigration mechanism across the BBB is poorly understood. In fact, potential for teratogenicity is a major concern [91].


Macrophages have numerous advantages as a brain delivery tool. They appear to be the natural choice as a cellular/biological vehicle for the delivery of nanoparticles into the CNS for a variety of reasons. First, to maintain brain homeostasis, routine trafficking of macrophages occurs through BBB. However, during neuroinflammatory conditions, a high turnover rate of macrophages ensues (30% in 90 days) leading to higher uptake into the CNS. Second, under normal physiological conditions, monocytes/macrophages can traverse the BBB through highly regulated paracellular diapedesis and also through less well-defined transcellular diapedesis. It is a process ofmovement by which leukocytes escape out of the circulatory system and travel toward the site of tissue damage or infection. Such transmigration of macrophages occurs into the brain without any structural damage to the BBB. Third, macrophages are attracted and infiltrated into the brain during inflammation and tumor growth. This mechanism can render them as potential delivery vehicle carrying therapeutic nanoparticles for the treatment of CNS disorders including malignant gliomas. Finally, macrophages are responsible for carrying out the natural function of phagocytosis of foreign bodies. This property enables macrophages to entrap a variety of nanocarriers including therapeutic, diagnostic, and imaging agents, which are otherwise restricted by the BBB [92—94].

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