Endothelial Cells & Capillary Leak - The Pierce Lab at Yale School of Medicine

Transcript

• 00:05The endothelial cells line every single vessel of the body
• 00:08from the large aorta that pumps blood out of the heart
• 00:11to even the capillary cells that get one tenth the size of a human hair,
• 00:16and so it's the endothelial cells that are in contact with the blood
• 00:20that regulate the blood flow, the platelet activation, the immune cell activation.
• 00:24There's at least 11 different types of endothelial cells in the lung alone.
• 00:29The heart probably has six different types of endothelial cells
• 00:32and what's important for me is that all of these endothelial cells
• 00:35respond differently to infection or trauma.
• 00:43My lab focuses on blood vessel dysfunction in critically ill children,
• 00:47and we're keen to really understand how to diagnose
• 00:50the differences between endothelial cell activation,
• 00:54which is generally a helpful process to stop blood bleeding where a cut is,
• 00:59or to bring immune cells to where an infection is,
• 01:01from endothelial cell dysfunction, which is bad,
• 01:04which allows too much bleeding or recruits too many or not enough immune cells.
• 01:10We're especially focused on how the endothelial cells regulate the vascular barrier.
• 01:15When someone becomes critically ill,
• 01:16their hands and their face get all swollen.
• 01:18That swelling happens in their organs too,
• 01:21and that leads to the organs not working properly
• 01:24and so my lab exists to undetstand
• 01:27how this phenomenon called capillary leak,
• 01:29where blood volume leaks from inside the blood vessel space
• 01:33to outside the blood vessel space, happens.
• 01:42It's very challenging because endothelial cells are on the inside of the blood vessels.
• 01:46So they're hard to study.
• 01:47But my lab starts with a highly translational process.
• 01:50We get samples at the bedside of critically ill children,
• 01:54whether it's blood, lung fluid
• 01:56or actually we found a way to collect individual endothelial cells and analyze them
• 02:02and identify processes or targets that we can then study in cultured endothelial cells
• 02:08and collections of cells that are known as organoids.
• 02:12From that analysis, has been very, very illuminating and telling of what
• 02:17endothelial cells are doing in the blood vessels of critically ill children
• 02:26Ultimately, we want to be able to diagnose and treat capillary leak
• 02:30and capillary leak makes every disease process worse,
• 02:33and so if we had tools that could diagnose it,
• 02:36we could better triage the organ support that we provide,
• 02:40whether it's a breathing machine
• 02:42or medicines to make the heart beat faster and stronger,
• 02:44and ultimately we want to be able to treat it to give a medicine or a therapy
• 02:49that reduces the amount of blood volume leaking out into the tissues.
• 02:54I was motivated to conduct research based on my experiences at the bedside,
• 02:58and would have children come in that were critically ill,
• 03:02and we would see them get swollen
• 03:03and we would see their organs fail,
• 03:05and we had no tools to diagnose it, no new treatments.
• 03:08So I became inspired to research capillary leak
• 03:11from my clinical experiences of critically ill children.
• 03:15That translational approach still motivates us today.