Reporting in today's edition of the journal Transplantation, lead author Dani Zander, M.D., of The University of Texas Medical School at Houston, and colleagues at the University of Florida College of Medicine found that less than 1 percent of a certain type of reparative lung stem cell originated in the bone marrow of the transplant recipient.
"It's possible in the future that circulating stem cells could be augmented to play a greater role in lung repair – and people are looking at ways to do that. We found that the bulk of stem cell contribution to the repair process belongs to those stem cells normally found in the lungs rather than to circulating stem cells," said Zander, who is professor and vice chair of pathology and laboratory medicine.
Stem cells are produced during adulthood in the bone marrow, where some remain while others circulate in the blood stream. Their main function is to produce all of the elements of blood. Some studies show that circulating stem cells are capable of diffentiating into other types of tissue, including lung tissue, Zander said, and this study provides evidence of differentiation.
Researchers examined lung biopsy specimens from seven male transplant recipients who had received lungs from female donors. They analyzed the origins of type II pneumocytes, a stem cell involved in the complex processes of lung repair, found in the lung tissue. Donor lungs come with their own type II pneumocytes, which in this case have two X chromosomes. Cells produced by the recipient's bone marrow have an X and a Y (male) chromosome.
Lung transplant recipients are vulnerable to pulmonary injury from infections, rejection of the transplanted lung, ischemia, and other factors that damage the alveoli – tiny hollow sacs along the airways where the blood takes in oxygen and discards carbon dioxide.
The processes by which alveoli recover from damage are complex and incompletely understood, Zander said. Previous research showed that type II pneumocytes in the lungs are known to play a central role, but the role of the bone marrow-derived version of the cells is less clear.
"The lung has received relatively little investigation in this area," Zander said. "It's a challenging organ to study because the air-tissue interfaces make it difficult to separate different cell types."
Applying advanced research techniques that previously had been used to analyze liver and bone marrow transplant recipients, the team found that nine of 25 lung tissue specimens from five recipients contained small numbers of the male gender version of the type II pneumocytes. The proportion of Y chromosome-containing pneumocytes was less than 1 percent.
They also found a statistically significant relationship between the number of Y chromosome-containing pneumocytes and the incidence of acute cellular rejection in the tissue, suggesting that stem cell repopulation might be stimulated by greater degrees of injury to the lung.
The possibility that the presence of male gender pneumocytes in female lungs might result from an earlier pregnancy with a male fetus cannot be ruled out, Zander said. However, the association between the number of those cells found in the lung tissue with damage from rejection makes that unlikely.
There was no sign of fusion between the bone marrow-derived cells and the donor pneumocytes, said Zander, who holds the Harvey S. Rosenberg, M.D., Chair in Pathology and Laboratory Medicine at the medical school and serves on the Council of the American Society of Investigative Pathology, a prestigious organization focused upon investigating mechanisms of disease. She also was awarded the Young Clinical Scientist Award this year by the Association of Clinical Scientists.
Study co-authors are Maher Baz and Christopher Cogle both of the Department of Medicine; Gary Visner of the Department of Pediatrics and senior author James Crawford, of the Department of Pathology, all at the University of Florida College of Medicine in Gainesville, Fla., and Neil Theise of the Department of Pathology at Beth Israel Medical Center in New York.
Journal
Transplantation