Synopsis: In the 1st episode in our 3-Part Series on Ways to Attack Pulmonary Vascular Disease, Stanford researchers Astrid Gillich, PhD and Ross Metzger, PhD explore the basic science approach and discuss their discovery of two capillary cell types. Astrid Gillich, PhD Ross Metzger, PhD Host:Welcome to the PH at Stanford Podcast. This new podcast series comes to you from the Vera Moulton Wall Center for Pulmonary Vascular Disease at Stanford, with the goal of addressing specific research efforts, educational programs, and advancements in treatment and patient care. Today, is the first in a three-part COVID-related series on Ways to Attack Pulmonary Vascular Disease. Stanford researchers, Astrid Gillich, PhD and Ross Metzger, PhD, will be giving us a closer look at our lungs, discussing their discovery of two capillary cell types, as they explore the basic science approach of their research. Astrid Gillich, PhD:Hello, everyone. My name is Astrid Gillich. I'm a basic scientist at Stanford University. I am part of the Wall Center for Pulmonary Vascular Disease and today I am very excited to talk to you about our work on the blood vessels of the lung. Ross Metzger, PhD:Hi, I'm Ross Metzger. I am also a researcher doing basic research in the Wall Center at Stanford. I began studying the lung more than 20 years ago as a graduate student in the lab of Mark Krasnow who's now the executive director of the Wall Center. And the work that we're going to tell you about is a collaboration between my lab and Mark's. Astrid Gillich, PhD:Our lung is really important, because it functions to bring oxygen into our body, which we need for our cells to survive and function properly. The lung has an extremely complicated architecture to accommodate a really large surface, about half the size of a tennis court. With every breath we take, air enters our lung and travels through a series of branched tubes, and there are literally millions of them, to the interior of the organ, where it reaches tiny air sacs called alveoli. Here, oxygen is transferred across an extremely thin membrane into the blood, and is carried by red blood cells to every part of our body. We refer to this process where oxygen moves into the blood and carbon dioxide is eliminated as gas exchange. The alveoli are the sites of gas exchange. So what is an alveolus? An alveolus is essentially a tiny pocket with an opening in walls that are extremely thin to allow efficient transfer of oxygen into the blood. The pocket is made up of cells. These are epithelial cells and we know that there are two types, and they have very distinct structures and functions. Each of these pockets is surrounded by a network of tiny blood vessels, the capillaries. The capillaries are tubes, they are composed of endothelial cells, so they are the cells that make up the walls of the vessels and they are filled with blood. The two layers of cells, the endothelial cells of the capillaries, and the epithelial cells of the alveolus are closely aligned to form the air-blood barrier. The structure of the air-blood barrier is altered and gas exchange is compromised in many different lung diseases, including acute diseases, chronic diseases, and including COVID-19. Ross Metzger, PhD:Alveoli were discovered in the 17th century by Marcello Malpighi in Bologna in Italy. Malpighi was using the microscopes of his time when he made these remarkable drawings of the alveoli. What he was really fascinated by, and you can really see this in the drawings, is the architecture of the alveoli, this remarkable structure of the lung. He was really the first to appreciate that. He was interested in trying to understand from what he could see what he could learn about the function of the lung. Malpighi was not only the first to discover the alveoli, but he was the first to discover and he also drew the capillaries surrounding these pockets and that work really inaugurated lung biology, basic research into understanding the structural basis of lung function. Of course, since Malpighi, there have been remarkable advances. We have a great understanding of the physiology of the lung. A lot of this has been made possible by technologies that didn't exist in the 17th century. Even the structure of the air-blood barrier, the cellular basis for gas exchange, has been really carefully worked out. These are discoveries that have saved lives, and these are the discoveries that can now be found in the textbooks. When we started our work, the alveolar capillaries, on the blood side of the air-blood barrier, had been much less well studied than the epithelial cells on the air side. According to this textbook account of the lung, there's a single capillary cell type in the alveolar capillaries, and that in fact is thought to be true for capillaries or really blood vessels throughout our bodies. In blood vessels people had thought that cells that sit next to each other were the same cell type, and that's different from...
