Pulmonary macrophage transplantation therapy
Takuji Suzuki1, Paritha Arumugam2, Takuro Sakagami1
1Division of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
Nature
|October 3, 2014
Summary
Pulmonary macrophage transplantation (PMT) offers a safe, effective therapy for hereditary pulmonary alveolar proteinosis (hPAP) without myeloablation. This cell therapy corrects lung disease and prevents mortality, with lasting effects observed.
Area of Science:
- Immunology
- Cell Therapy
- Pulmonary Medicine
Background:
- Bone-marrow transplantation is effective but carries risks due to myeloablation.
- Resident macrophages self-maintain independently of hematopoietic progenitors.
- Hereditary pulmonary alveolar proteinosis (hPAP) is a severe myeloid disorder in children.
Purpose of the Study:
- To evaluate pulmonary macrophage transplantation (PMT) as a cell therapy for hPAP.
- To assess the safety and efficacy of PMT without myeloablation.
- To investigate mechanisms of alveolar macrophage regulation.
Main Methods:
- Utilized granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor-β-deficient (Csf2rb(-/-)) mice modeling hPAP.
- Administered wild-type or gene-corrected macrophages via PMT.
- Monitored disease correction, biomarker normalization, and survival.
Main Results:
- PMT was safe and well-tolerated in Csf2rb(-/-) mice.
- A single PMT administration corrected lung disease and systemic manifestations.
- Therapeutic effects and persistent alveolar macrophages were observed for at least one year.
- Disease-related biomarkers normalized and disease-specific mortality was prevented.
Conclusions:
- PMT is a potential first-in-class therapy for hPAP.
- GM-CSF is crucial for alveolar macrophage phenotype determination.
- Findings support PMT translation for treating children with hPAP.
