Yale University researchers have reported an important first step in regenerating fully functional lung tissue that can exchange gas ““ the most critical function of the lungs.
Lung tissue is difficult to regenerate because it does not generally repair or regenerate beyond the microscopic level.
Currently, the only way to replace damaged adult lung tissue is through lung transplantation, a procedure highly vulnerable to organ rejection and infection, and one in which the ten-year survival rate is just 10% to 20%.
The Yale researchers sought to determine if it was possible to successfully implant tissue-engineered lungs, cultured in vitro, that could serve the lung’s primary function of exchanging oxygen and carbon dioxide.
Working with adult rat lungs, they removed the existing cellular components while preserving the extracellular matrix and hierarchical branching structures of the airways and vascular system, which were later used as scaffolds to grow new lung cells.
The researchers then cultured a combination of lung-specific cells on the extracellular matrix, using a unique bioreactor that mimicked some aspects of fetal lung environment.
When implanted into rats for short intervals of time (less than two hours), the engineered lungs exchanged oxygen and carbon dioxide similarly to natural lungs.
“We succeeded in engineering an implantable lung in our rat model that could efficiently exchange oxygen and carbon dioxide, and could oxygenate hemoglobin in the blood. This is an early step in the regeneration of entire lungs for larger animals and, eventually, for humans,” said Laura Niklason, M.D., Ph.D., professor and vice-chair of the Departments of Anesthesiology and Biomedical Engineering at Yale University and lead author of the study.
The researchers found that the mechanical characteristics of the engineered lungs were similar to those of native tissues and, when implanted, were capable of participating in gas exchange.
“Seeded and cultured epithelium displays remarkable hierarchical organization within the lung matrix, while seeded endothelial cells efficiently repopulate the lung vasculature,” said Niklason, a member of the Yale Medical Group.
The Yale team said that while this is an important first step, more research must be conducted to determine if fully functional lungs can be regenerated in vitro, implanted and sustained in their functioning.
It is likely that years of research with adult stem cells would be required to repopulate lung matrices and produce fully functional lungs, said Dr. Niklason, who added it may take 20 to 25 years before scientists can adopt a create-an-organ approach for humans.
Some 400,000 people lose their lives each year in the United States from lung disease. Lung tissue is difficult to regenerate because it does not typically repair or regenerate beyond the microscopic level.
The work was reported online Thursday in the journal Science Express.
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