Encapsulation of mesenchymal stem cells as a potential treatment for stroke, modeled as an oxygen glucose deprived system

During a stroke there is a reduction of oxygen, glucose, and other nutrients to the surrounding brain tissue causing neuronal death and astrocyte activation. Astrocytes are responsible for protecting the neurons during an injury. Part of the astrocyte activation is the release of various molecules as well as a change in morphology from a polygonal to a stellate state. Astrocyte’s morphological change can eventually lead to a glial scar preventing neurons from reforming connections. Obtaining an effective therapeutic to reduce the negative effects of astrocyte activation could greatly enhance recovery after a stroke. Mesenchymal stem cells (MSCs) have numerous anti-inflammatory and neuroprotective properties and with further development may be developed into an effective therapeutic. MSCs have been shown to regulate the immune response by reducing inflammatory molecules, such as TNF-α. However, there are several limitations with MSCs that must be addressed first, such as low viability, differentiation, and migration away from the injury site. To overcome these limitations the MSCs are encapsulated in alginate. The encapsulation still allows for soluble factors to interact with the MSCs and the host tissue while maintaining viability, keeping the MSCs undifferentiated, and allowing for localization to the injury site. In previous experiments, using encapsulated MSCs, attenuation of neuro-inflammation was achieved by PGE2 secreted by the MSCs. With the encapsulated MSCs, the MSCs can be used as a therapeutic. Stroke is one injury that has few treatments where MSCs could be beneficial. In vitro stroke is modeled as an oxygen glucose deprived system. Rat cerebral astrocytes are plated into a 24 well plate and exposed to 1% O2 and no glucose for 2.5, 5, or 10 hours. Astrocytes are then placed into normoxia conditions and recover for 24 hours. Increased expression of GFAP and elongation of astrocytes, measured by perimeter over area signify a change to a reactive state. There is a significant difference (p