Nuclear Rupture in Progeria Expressing Cells

Cells regularly take on various types of force in the body. They have structures that are able to mediate, transfer and respond to the forces. A mutation in force regulating proteins such as lamin in the nucleus or the KASH domain which connects the nucleus to the cytoskeleton of the cell can cause catastrophic events to occur. The aims of this study were to better understand the response of the nucleus when structural proteins are mutated or are not present while under force. Progeria, a rare disease where an additional farnesyl group is attached to lamin was used in this study. Different types of forces were used to represent similar conditions in the body. Confinement of endothelial cell width showed an increase of surface defects. When restricting proteins such as actin was removed the nucleus appeared to rupture. This was shown to occur at a higher rate in the progeria groups. Endothelial cells under shear force showed high amount of nuclear rupture in progeria expressing group. prolonged exposure showed more rupture which eventually cased cell death and cells to come off the surface. Progeria expressing smooth muscle cells under cyclic stretch also showed similar results as endothelial cells. The amount and rate of deformation of the nucleus when the cytoskeleton is connected and not was looked at. When the connected the rate of deformation was higher. The high rate of nuclear defects and rupture while under force in progeria expressing cells shows that the nuclei have different structural properties and are weaker. It’s also been shown that the LINC complex contributes to nuclear deformation when stretching

Pulmonary Patency Stent

Patients with malignancies in the central airways often experience significant breathing difficulties due to occlusion of the airways. One common palliative treatment option for this is a stent placement procedure. While patients often experience immediate symptom relief, long term use can result in the formation of granulation tissue, causing restenosis of the airway. The objective of this project is to design and prototype a modification to the Boston Scientific Ultraflex partially-covered stent in order to reduce granulation tissue and maintain airway patency. Deliverables include the detailed design, a working prototype, and supporting data. The main product specifications include effectiveness in reducing granulation, coating adhesion, and stent stability. The final design for this product consists of a paclitaxel-SIBS coating placed at the uncovered ends of the stent by using a dip coating method. This coating was tested in many ways, including for its effectiveness in reducing cell attachment, release kinetics, coating stability, and cytotoxicity. This testing has shown that the SIBS-paclitaxel coating is effective in reducing cell attachment in-vitro, the coating is stably adhered onto the stent in a moving environment, and that paclitaxel is steadily released from the coating. These results are very promising for future in-vivo studies.https://scholarscompass.vcu.edu/capstone/1077/thumbnail.jp