Researchers at the University of Illinois at Chicago (UIC) College of Medicine say that bone marrow derived progenitor cells require integrin-mediated adhesion to effect protection in a mouse model of acute lung injury (ALI). They report the identification and use of adult stem cells from bone marrow, called Flk-1 and CD34, even though they are present in small quantities.
The study is published online in the October issue of Stem Cells. The paper is titled “Requirement of α-4-β-1 and α-5-β-1 Integrin Expression in Bone-Marrow Derived Progenitor Cells in Preventing Endotoxin-Induced Lung Vascular Injury and Edema in Mice.”
In ALI, the layer of cells that forms the lining of the blood vessels surrounding the lung's air sacs is damaged, allowing fluid to leak in and fill the sacs. Repair of these breaks in the endothelium is complicated by the fact that endothelial cells are long-lived, says Kishore Wary, Ph.D., UIC assistant professor of pharmacology and lead author of the study. Turnover of new cells takes as long as two to five years, and few of the precursor cells needed for replacement circulate in the body at any given time. “The stem cells that might be able repair the damage caused by ALI are simply not on hand,” Dr. Wary says.
Flk-1 and CD34, named for the proteins on their surfaces, constitute a very small percentage of the stem cell population in the bone marrow, but the researchers were able to develop a way of culturing the cells that increased their numbers and their stickiness. The stem cells stud their surface with molecules called integrins that allow the cells to stick to their targets and affect the repair. “Increasing this capacity for stickiness in our culture system was likely to make the stem cells more effective in repair,” Dr. Wary explains.
When mice that had been injected with a compound that causes ALI were injected with the purified and cultured Flk and CD34 stem cells, the progenitor cells were able to repair the lung injury and prevent fluid build-up, and this led to improved survival.
The mouse disease model not only demonstrated that stem cell treatment is a promising therapy for ALI, Wary notes, “but also provided us with the means to understand how these progenitor cells did their repair work. These therapeutic cells employed integrins to stick to the site of injury and turn on cellular and molecular repair machinery.” The researchers hope to explore the possibility of using stem cell therapy in human acute lung injury.