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| Micrograph of pulmonary alveolar proteinosis--Courtesy of NIH |
Using a new type of cell transplantation, researchers at Cincinnati Children's Hospital Medical Center corrected a lung disease in mice that mimics a similar rare condition in humans.
The findings could provide the basis for new therapies that treat human lung diseases caused by dysfunctional immune cells.
Detailed in a study published Oct. 1 in Nature, the researchers focused on macrophages, a type of immune cell that helps collect and remove used molecules and cell debris from the body.
They transplanted either normal or gene-corrected macrophages into the respiratory tracts of mice, which were bred to have a rodent form of lung disease called hereditary pulmonary alveolar proteinosis (hPAP). After being treated with both normal and gene-corrected macrophages, mice recovered from the disease.
"Our findings support the concept of pulmonary macrophage transplantation (PMT) as the first specific therapy for children with hPAP," said Dr. Bruce Trapnell, senior author and a physician in the Division of Neonatology and Pulmonary Biology at Cincinnati Children's, in a statement.
The results also revealed mechanisms that regulate the numbers and type of macrophages that are present in tiny air sacs of the lungs--called alveoli--in healthy lungs compared to those in a diseased state.
In hPAP, the air sacs become filled with surfactant, a substance the lungs produce to reduce surface tension and keep the air sacs open.
Previous research has shown that children with hPAP have mutations in the CSFR2RA or CSFR2RB genes, which hinder the ability of macrophages in the air sacs to remove used surfactant from the lungs. This used surfactant builds up in the lungs, filling the air sacs, resulting in breathing difficulties, and in severe cases, respiratory failure.
Working off this knowledge, researchers tested a cell therapy designed to restore the Csf2rb gene in mice with a dysfunctional one. Investigators packaged the therapy in a viral vector engineered to deliver a correct version of Csf2rb to abnormal macrophages in the alveoli. The gene-corrected cells were then administered back to the mice and injected into the lungs. The therapy corrected the lung disease, was well tolerated and prevented mortality associated with the disease for at least one year.
The team is now conducting further preclinical studies of the gene therapy to determine whether it could be safety tested in humans.
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- read more from Cincinnati Children's Hospital
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