 Hi, I'm Tyler Allen, a PhD student at North Carolina State University in Comparative Biomedical Sciences. Today, I'm going to be talking to you about angiopelosis, an alternative mechanism of cell extravasation. Angiopelosis represents an alternative mechanism of cell extravasation. In this method, the cell will travel through the bloodstream and then attach to the blood vessel wall. The endothelial cells of the blood vessel will then actively wrap around the cell and remodel and push it from the inside of the lumen into the surrounding tissue where it can exert its beneficial and regenerative effects. This is in stark comparison to white blood cell extravasation. White blood cells are leukocytes extravasate in a well characterized manner known as dipedesis. In this method, the cell squeezes in between two endothelial cells into the surrounding tissue, usually as an immune response. We discovered this phenomenon while trying to answer a simple question, and that question was how do stem cells, when injected intravenously, cross the blood vessel wall and enter surrounding tissue? As a promising method for stem cell therapy, stem cells are directly infused intravenously into the bloodstream and have shown to have the potential to migrate their home in on damaged or inflamed tissue and then cross the blood vessel wall to enter that inflamed or damaged tissue where it can then exert its therapeutic or regenerative effects. So, to study this, we used a system where blood vessels or vasculature express green fluorescent protein. We then directly injected stem cells that were labeled with a fluorescent marker directly into the bloodstream and then using intravital light sheet microscopy, we saw in real time the exact mechanism that these cells used to extravasate. We have observed that stem cells undergo a multi-step process to extravasate when directly injected into the bloodstream. First, the stem cell will travel through the bloodstream where it then becomes enlarged or attaches into the blood vessel wall. Once attached, the blood vessel wall will then extrude protrusions around the cell and then remove it from the lumen into the surrounding tissue. Once in the surrounding tissue, it can then exert its regenerative or therapeutic effects. Using intravital light sheet microscopy and 3D rendering, we're able to see exactly where the cell is in relation to the blood vessel and the vasculature and the method that it uses to extravasate. Here, we have a time lapse image of a stem cell undergoing angiopollosis. In this video, the stem cell is actively being pushed from the lumen of the blood vessel into the surrounding tissue where it can then exert its beneficial or therapeutic effects. Through this study, we have characterized a previously unreported method of cell extravasation that differs distinctly from diapodesis, both temporally, mechanistically, and molecularly. If you have further questions or would like to talk about this more, please contact either myself or my advisor, Dr. K Chang. Thank you.