TUESDAY, Aug. 3, 2004 (HealthDayNews) -- New research holds out hope for people suffering from pulmonary fibrosis, a deadly lung disease, by discovering that cells that travel to the organ to repair damage end up doing more harm than good.
The study found these biological repairmen, which experts had thought originally resided in the lungs, were actually adult stem cells that migrated there from the patient's bone marrow -- and this migration can be halted.
The discovery may help people suffering from other conditions that, like pulmonary fibrosis, involve the excessive formation of scar tissue, experts said.
As it stands now, however, the research is still in its infancy.
"It's certainly very exciting research, but the information is obviously very preliminary," said Dr. Alfred Munzer, a lung specialist from Maryland and past president of the American Lung Association. "We have to see what meaning it holds."
Pulmonary fibrosis is a chronic and often fatal disorder that is characterized by extra scar tissue in the lungs. The disease, which affects some 80,000 individuals in the United States, has traditionally been treated with steroids and other immunosuppressive therapies, but with little effect. About 70 percent of people die within five years of diagnosis. "At the moment, there is no effective treatment for pulmonary disease, and it is not that uncommon a disease," Munzer said.
Scientists had believed the condition was caused by cells called fibroblasts and myofibroblasts that were already located in the lung. "The classical concept of repair is that you have cells within the local environment which can migrate into the site of the injury and which have the ability to contract the wound and increase the amount of material that repairs that wound like collagen," said study author Dr. Robert M. Strieter, chief of pulmonary and critical care medicine at the University of California at Los Angeles David Geffen School of Medicine.
Later on, scientists realized that cells in circulation in the bloodstream actually migrated to the injury to help repair it. The only problem was that the repairs themselves ended up being destructive. "The lung is an organ that likes to be filled with air, not scar tissue, so the lung doesn't function very well," Strieter said.
Now Strieter and his colleagues, reporting in the Aug. 2 issue of the Journal of Clinical Investigation, have identified these traveling cells as adult stem cells from the bone marrow. In a mouse model, they have also managed to stop them from traveling to the lung where they contribute to the onset of the disease.
The researchers injected these human stem cells into an immunodeficient mouse and demonstrated that the cells traveled to the lungs when there was an injury.
Next, they demonstrated that mouse cells did the same thing. "They could actually traffic and hone to the lung under conditions of injury and contribute to the fibrotic process," Strieter said.
How did they make the lung their destination? A specific receptor on the cells interacted with a specific ligand (which binds to the receptor) to pull the cells towards the lungs. "It's a way to target these cells to a specific area," Strieter explained.
The next step was to use an antibody to target the ligand, thus blocking "recruitment" of the cells and also the development of fibrosis.
While the technique holds promise for pulmonary fibrosis, it also holds hope for people suffering from connective-tissue diseases such as rheumatoid arthritis and liver cirrhosis.
"These cells are not unique to the lung," Strieter said.
Although more research needs to be done, results may come sooner than expected, as there are already drugs that target this receptor-ligand pair.
The particular receptor under investigation here (CXCR4) is also involved in HIV. Specifically, "HIV strains that target T-cells use this receptor as a co-receptor to infect T-cells," Strieter said. "The discovery of its association with AIDS has propelled the pharmaceutical field to make discoveries that may be useful not to treat AIDS, but to treat this."
More information
For more on pulmonary fibrosis, visit the Pulmonary Fibrosis Foundation.
